Objective To study the prognosis of IgA nephropathy(IgAN). Methods Forty-six out of 780 IgAN patients biopsied in a single unit of north China since 1997 showed segmental necrotizing lesions. Thirty-five of these patients were followed up for (26±26) months after biopsy. Their morphological features and natural history were compared with those of control group of 80 patients without segmental necrosis， who had comparable serum creatinine with a follow-up for (39±23) months. Progression was indicated as 50% elevation of serum creatinine or 33% decline of Ccr or development of ESRD. Their clinical outcomes were compared using Kaplan-Meier estimation. Cox regression was performed to identify predictive factors for clinical events. Results Only 2 necrotizing patients showed ARF. No difference was found in the clinical symptoms presented. The necrotizing group showed a more significant accumulation of monocytes and lymphocytes (P = 0.004) with lower percentage of glomerular sclerosis (P = 0.002). Among the groups of follow-up shorter than 24 months， 3 of 22 necrotizing IgAN patients and 1 of 28 non-necrotizing IgAN patients had futher progression (P = 0.08). In other groups， all necrotizing IgAN patients were event-free， 13 of 52 non-necrotizing IgAN patients progressed， in which necrotizing lesion was not an independent risk factor. Multivariate analysis showed that lesions with severe chronic background were the only prognostic factors (RR = 23.13， P < 0.01)， indicating prognosis was associated with the severity of universal lesions， not with necrotizing lesions alone. Conclusions Based on the present data， necrotizing lesion is not an independent risk factor and may not require aggressive therapy. Longer period of follow-up is needed for further confirmation.

Objective To investigate the role of urine albumin from nephrotic syndrome patients on expression of endothelin(ET)-1 in human proximal tubular epithelial cells (HK-2). Methods Proteins were precipitated with polyethylene glycol， and albumin were purified by Sephadex-75 column chromatography from urine taken from nephrotic syndrome patients. The HK-2 cells were divided into two groups: one group incubated with the urine albumin from nephrotic syndrome patients， another with HSA. The expression of ET-1 mRNA of HK-2 cells was assessed by RT-PCR， and the level of ET-1 protein was assessed by indirect immunofluorescence. Results The urine albumin and HSA up-regulated the expression of ET-1 mRNA and protein in HK-2 cells. The expression of ET-1 protein was associated with the stimulation time， and increased in dose-dependent manner. The expression of ET-1 mRNA in HK-2 cells increased significantly when cultured with urine albumin (0.5 mg/ml) from nephrotic syndrome (P < 0.05). However， only when the HK-2 cells were cultured with HSA at 2.5mg/ml， the ET-1 mRNA were markedly increased. Conclusion The urine albumin from nephrotic syndrome patients and normal serum albumin can up-regulate expression of ET-1 in HK-2 cells， and the urine albumin stimulates ET-1 synthesis by HK-2 cells to a higher extent as compare to that of normal serum albumin.

Objective To investigate a possible relationship between CD2AP mutation and focal segmental glomerulosclerosis (FSGS). Methods Genomic DNA from peripheral blood cells of FSGS patients were extracted， and CD2AP mutation was analyzed by polymerase chain reaction (PCR) and direct sequencing. Immunofluorescence staining， confocal laser scanning microscopy and LSM-510 graphic system were used to detect the expression and distribution of protein， including both CD2AP and podocin， in patients with CD2AP mutation. Eighty-two Chinese patients with idiopathic FSGS， including 43 males and 39 females whose age ranged from 12 to 76 years old were enrolled in this study. Of these， 55 had nephrotic syndrome (NS). Sixty genomic DNA from 60 healthy volunteers were selected as normal control group. Results (1) Two CD2AP heterozygous mutations were detected in exons. One was 160G > A in exon 2， which caused the 54th amino acid changed from valine to isoleucine， and occurred in one non-NS patient with renal failure. Another was 358A > G in exon 4， which caused the 120th amino acid changed from isoleucine to valine， and occurred in one NS patient with normal renal function and relapse twice. The same mutations were not found in the control group of 60 healthy people. (2) A decreased expression was observed in glomeruli stained with CD2AP antibody， accompanied with decreasing of podocin， in the patients with CD2AP mutation. (3) Moreover， 2 mutations in introns， 1 in promoter region and 1 SNP were first reported. Conclusions The mutations in CD2AP may cause FSGS in both NS and non-NS patient. The decreasing expression of CD2AP resulting from CD2AP gene mutation may affect the expression of podocin.

Objective To explore the relation between specific pathological features and clinical data in diabetic patients with renal damage. Methods Pathological features and clinical data were retrospectively analyzed in 64 diabetic patients with renal damage who underwent renal biopsy from 1992 to 2002. The pathological profiles were simultaneously compared with biopsies from non-diabetic patients during the same period. Results Patients were primarily divided into 3 groups according to their pathological features: the diabetic nephropathy (DN) group (42 cases， 65.6%)， the arterio-arteriolosclerosis and ischemic glomerular damage (BNS) group (6 cases， 9.4%)， and the primary glomerulonephritis (CGN) group (16 cases， 25.0%)， including 2 patients with glomerulonephritis superimposed on diabetic glomerulosclerosis. The specific pathological profiles of the CGN group were as following: IgA nephropathy 6 cases(37.5%)， focal segmental glomerulosclerosis (FSGS) 6 cases(37.5%)， minor change renal disease (MCND) 2 cases(12.5%)， and membranous nephropathy (MN) 2 cases (12.5%)， which were similar to those of non-diabetic patients， except that the ratio of FSGS was significantly increased (27.3% vs. 4.7%， P < 0.01). Linking with clinical data， DN and BNS groups had a longer diabetic duration than the CGN group (P < 0.05). The age of CGN groups was younger than that of other two groups (P < 0.05). No differences were showed in glucose and blood pressure levels among three groups. The amount of proteinuria in BNS group was significantly less than that of DN and CGN group[(0.45±0.33) g/d vs. (3.18±2.40) g/d and (2.68±1.27) g/d， P < 0.01]， and the latter two groups were not different. Similarly， the retinopathy incidence of the BNS group was markedly lower than that of DN and CGN group (0% vs. 38.1% and 37.5%， P < 0.01)， and no difference was found between DN and CGN group. Conclusions The CGN incidence in diabetic patients with renal damage is 25%， and its pathological profiles are similar to those of non-diabetic patients. Diabetic patients with renal damage should undergo early renal biopsy to differentiate DN and CGN， which would be beneficial for patients’ individual treatment.

Objective To study the effects of oxidants on the structure of albumin. Methods Using both AOPPs and protein carbonyl content as indices. The oxidative stress level in normal controls and uremia patients was evaluated. Albumin in plasma was purified by HPLC and then was subjected to amino acids composition assay. Results Both AOPPs level and protein carbonyl content in uremic patients were significantly higher than those in controls (P < 0.01). Most amino acids’ levels in albumin from uremic patients were down-regulated by 10% compared to the controls. A statistically significant difference of both cysteine and arginine in albumin was found between controls and uremic patients (P < 0.05). Conclusion The extensive loss of amino acids in uremic patients may play a pivotal role in affecting the structure and biological functions of albumin， provided that both cysteine and arginine are the major targets attacked by free radicals.

【Abstract】 Objective To dynamically observe the expression of slit diaphragm complex molecules, including nephrin, podocin, CD2AP, and cytoskeleton protein α-actinin-4, in adriamycin-induced nephrotic (ADN) rats, and to further explore the molecular behavior of podocyte proteins during the occurrence and development of proteinuria and their possible mechanisms. Methods Adriamycin nephropathy was induced by a single tail intravenous injection of adriamycin. Renal tissue samples were collected at day 3, 7, 14, and 28, respectively. The distribution, mRNA expression and protein expression of nephrin, podocin, CD2AP and α-actinin-4 were examined by indirect immunofluorescence, real-time PCR and Western blotting, respectively. Results (1) After the adriamycin injection, a significant increment of the 24-hour urinary protein was observed at day 14 and persisted up to day 28 (P < 0.01). (2) In ADN rats, the foot processes broadened to a different extent at day 14, and the diffuse fusion and effacement of foot processes were observed at day 28. (3) From the 7th day to the 28th day after adriamycin injection, nephrin and podocin staining gradually shifted from a linear-like pattern along the capillary loops of glomerulus to a discontinuous coarse granular pattern. Similarly, CD2AP shifted from an even GBM-like pattern to a coarse granular pattern, and α-actinin-4 changed from a dot linear-like pattern along capillary loops to a coarse granular pattern. (4) In ADN rats, nephrin mRNA expression was up-regulated at day 7 (P < 0.01) and returned to normal level at day 14 and 28. Podocin and CD2AP constantly increased from day 3 and reached a significant level at day 14 and day 28, respectively (P < 0.05). (5) The protein expression of nephrin started to increase at day 7 after adriamycin injection and was markedly elevated up to day 28 (P < 0.05). Likewise, compared with the control group, CD2AP protein expression of the ADN rats prominently increased at day 14 and persisted to day 28(P < 0.05). Interestingly, after the injection of adriamycin, podocin protein expression was dramatically upregulated at day 7 (P < 0.05), and thereafter recovered again, whereas it was significantly down-regulated at day 28 (P < 0.05). (6) Alpha-actinin-4 mRNA and protein expression showed no change at the time studied. Conclusion The increased expression of nephrin, podocin and CD2AP and their abnormal distributions are the molecular mechanism that leads to the occurrence and development of proteinuria in ADN rats. The enhanced expression may be a compensatory reaction of podocyte to injury.

Objective To design a method to characterize AOPPs. Methods Carbonyl groups were used as an oxidative index to link AOPPs and oxidized protein. Plasma-AOPPs were obtained by a series of preparation as follows. The native plasma was first determined for its protein contents followed by AOPPs level evaluation. Specimen was then washed with PBS and ultrafiltrated with an ultrafilter (10 000 cut-off membrane) to obtain clean plasma-AOPPs. A size-exclusion HPLC technique was used to verify which protein was oxidatively damaged. Fractions resulted from delipidation were also examined. Results The levels of AOPPs and total carbonyl groups in patient plasma were significantly higher than those in controls； both in native/delipidated plasma and CHCl3-resulted precipitate. HPLC revealed that serum albumin presented highest carbonyl levels. It was an exclusive protein with statistically significant difference between controls and patients (patients vs. controls in nmol carbonyl/mg protein: HSA:1.510±0.067 vs. 0.791±0.048， P < 0.01； Fg: 0.617±0.100 vs. 0.672±0.159， P = 0.773； IgG: 0.047±0.029 vs. 0.053±0.030， P = 0.791； Tf: 0.102±0.025 vs. 0.098±0.043， P = 0.385， respectively). Delipidation mainly removed fibrinogen and an unknown oxidized macromolecule. Conclusion Albumin is a more important contributor to AOPPs than other proteins， IgG in particular.

Objective To study the expression of angiopoietin-like protein 3(ANGPTL3)mRNA successively in kidney of adriamycin(ADR)-induced nephrotic rats during the development of proteinuria， and to disclose the possible assosiation of ANGPTL3 with proteinuria. Methods Adriamycin-induced nephrotic rat models were established by a single injection of adriamycin via the tail vein. Glomeruli and cortex tubuli of rats were dissected by laser microdissection. Real time quantitative RT-PCR was used to study the expression of ANGPTL3mRNA in kidney of ADR rats at 7， 14， 21 and 28 days successively following adriamycin injection. Results (1) In ADR rats， urinary protein and the level of triglyceride and cholesterol in serum increased significantly at day 14 (P < 0.01， 0.05 and 0.01， respectively)， at same time， serum albumin decreased significantly (P < 0.01). Changes of these indices reached the peak level at day 28. (2) Glomeruli and cortex tubuli of rats were dissected successfully by laser microdissection. (3) The mRNA of ANGPTL3 in total cortex of kidney in ADR rat increased significantly at day 21(P < 0.01) and at day 28 (P < 0.05) compared to that of control. (4) The tendency of ANGPTL3 mRNA expression in glomeruli of ADR rats was as the same as that in total cortex. ADR rats had a higher expression level of ANGPTL3mRNA in glomeruli at day 21 and day 28 compared to that of control (both P < 0.05). (5) There was no significantly change of ANGPTL3 mRNA expression in cortex tubuli following adriamycin injection. Conclusions ANGPTL3 mRNA can be expressed in the kidneys of normal and ARD rats. The expression of ANGPTL3 mRNA increases in glomeruli of ADR rats during the development of proteinuria.

Objective To explore whether LDL and oxLDL may induce kidney tubular epithelial-mesenchymal transition (EMT) and its mechanism. Methods The second generation human kidney tubular epithelial cells(TECs) were cultured for 24 hours in different conditions as (1)serum free as control， (2) treated with LDL(50 μg/ml)， (3) treated with oxLDL(50 μg/ml)， (4)treated with LDL(50 μg/ml) plus PD98059(5 μmlo/L)， (5) treated with oxLDL(50 μg/ml) plus PD98059(5 μmol/L). The expression of cytokeratin， E-cadherin， α-SMA and vimentin was assessed by immunofluorescence and Western-blot. Western-blot was also performed to test the expression of collagen I and phospho-ERK1/2MAPK and phospho-GSK-3β. Results oxLDL was more potently in inducing tubular EMT than LDL at 24 hours as demonstrated by de novo α-SMA expression， increased expression of vimentin， partial loss of cytokeratin and reduction of E-cadherin expression by TECs. The expression of collagen I and phospho-ERK1/2MAPK and phospho-GSK-3β was increased in TECs stimulated by LDL or oxLDL. MAPK inhibitor(PD98059) inhibited the phosphorylation of GSK-3β and almost completely blocked oxLDL-induced tubular EMT. However，PD98059 alone was able to inhibit LDL-induced tubular EMT partially. Conclusions oxLDL is more potently in inducing tubular EMT than LDL. The ERK1/2MAPK-GSK-3β signaling pathway mediates the LDL or oxLDL-induced tubular EMT.

Objectives To modify glomerular filtration rate (GFR) estimating equation (also called abbreviated MDRD equation) based on plasma creatinine (Pcr) and other demographic data from Chinese chronic kidney disease (CKD) population， and compare the diagnostic performance of the modified abbreviated MDRD equations with that of original abbreviated MDRD equation in different CKD stages. 

Methods Six hundred and eighty-four patients with CKD including 352 males and 332 females，with average (49.9±15.8) years，were collected from 9 renal institutes of university hospital located in 9 different geographic regions of China，and were enrolled in this study from June 2004 to September 2005. Four hundred and fifty-four cases were randomly selected to be included in the training samples， and the remaining 230 cases were used as testing samples. Using 99mTc-diethylene triamine pentaacetic acid(99mTc-DTPA) plasma clearance by dual plasma sampling method as reference GFR(rGFR)，the original abbreviated MDRD equation was modified by the following two methods. Firstly， a racial factor for Chinese was added to the original abbreviated MDRD equation. Secondly， multiple linear regression was applied to the training sample， and the coefficient associated with each variable in the original abbreviated MDRD equation was modified respectively. The modified equations were validated in the testing samples and were compared with the original abbreviated MDRD equation. 

Results Both modified abbreviated MDRD equations showed significant performance improvement in bias(the areas between the regression line of difference and a common distance along the zero difference line were 543.0， 677.2， and 2175.0 arbitrary units， respectively)， precision [the widths between the 95% limits of agreement for the regression line of difference were 57.5，56.5 and 60.7 ml▪min^-1▪(1.73 m²) ^-1， respectively]. Compared with the original abbreviated MDRD equation，the 30% accuracy of modified abbreviated MDRD equations was significantly higher(from 66.1% to 77.8% and 79.6%， P < 0.05). 

Conclusions Compared with original abbreviated MDRD equation，the modified abbreviated MDRD equations based on the Chinese CKD patients offer significantly advantages in different CKD stages. It can be applied to GFR estimation in substitution of original abbreviated MDRD equation.

Objective To evaluate the cost-effectiveness of intravenous and oral iron supplements in hemodialysis patients with chronic renal anemia. Methods Two hundred and thirty-five patients with renal anemia were enrolled and randomly divided into intravenous group(n=116) who received iron dextran injection and oral group (n=119) who received ferrous succinate tablets. The dosage of iron dextran was calculated for each patient and was given during each hemodialysis session. After total dosage was finished， 100 mg of maintenance dose was given periodically depending on the levels of ferritin and Hb. The oral group received ferrous succinate tablet equivalent to 200 mg element iron. Two hundred and twenty-six patients finished 26-week treatment and 113 patients in each group. HB and Hct were indexes to evaluate the efficacy of the treatment. The treatment cost included the direct medical costs in iron product， EPO， medical examination and adverse events， and indirect medical costs in traffic， nursing， nutriment and the loss of labor. Results The average treatment cost for each patient was 25 thousand yuan(RMB) and 24.1 thousand yuan(RMB) for intravenous and oral group respectively with no significant difference(P > 0.05). The effective rates were 88.5% and 71.68% for intravenous and oral group respectively with significant difference (P < 0.05). Therefore， average cost per patient for achieving effectiveness was 28.213 thousand yuan(RMB) and 33.683 thousand yuan(RMB) for intravenous and oral group respectively. Conclusions Intravenous iron therapy is more effective in the treatment of renal anemia. There is no significant difference in treatment cost between two groups. Therefore， intravenous iron dextran has greater cost-effectiveness than oral iron in renal anemia， and is worthy to be recommended to clinical application.

Objective To assess the efficacy of two antibiotic prophylactic regimens in a prospective randomized trial in 1 year for patients undergoing insertion of catheters， and to provide the evidence for uniform consensus existing on the timing， route， and choice of antibiotic. Methods During a period of 12 months， 78 patients， who consecutively entered the peritoneal dialysis programme， [45 women and 33 men， mean age (48.2±15.7)years] were included. The prophylactic regimens were a single dose of ceftriaxone (1.0 g) given intravenously 30 minutes before surgery (Group A) and given cefazolin (0.25 g/L) i.p. in the each dialysis bag for 3 days postoperatively (Group B). All operations were performed in one room. The wound was observed every day， and body temperature， Count of white blood corpuscle and type， dialysate were examined every day. Results In Group A and B， none of the patients showed peritonitis or wound infection during the post-operative period (within 10 days). One of 39 patients(2.5%) in the group A， and 2 of 39 patients (5.1%) in the group B had exit site infection (P > 0.05). Conclusions There is no significant difference in the incidence of peritonitis and wound infection between two groups. Prophylactic preoperative single-dose antibiotics intravenously do as well as antibiotics given intraperitoneally for peritoneal dialysis catheter insertion， but is much more convenient.

Objective To explore the distribution of dendritic cells(DCs) and the expression of adhesion molecules in rat kidney with unilateral ureteral obstruction(UUO)，as well as the regulatory effect of anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) on adhesion， maturation and function of human DCs cultured in vitro. Methods UUO rat models were established， which were divided into sham group(n=6)，untreated group(n=18)and treated group with PsL-EGFmAb(n=18). DCs were analyzed with Axioplan 2 microscopy， while P-selectin being observed by immunohistochemistry. CD34+ stem cells were isolated from cord blood and cultured in 20%IMDM medium with SCF， GM-CSF， TGF-β1， Flt-3L and TNF-α in vitro. During development， PsL-EGFmAb was added and IL-10 served as control. FACS was performed to detect the expression of HLA-DR， CD1a， CD11c， CD54，CD83， CD80， CD86， CD209 (DC-SIGN) and CD62-P，-E，-L(P-，E-，L-selectin) on DCs. RT-PCR was performed to detect the expression of NF-κB P50， P65 mRNA. MLR was performed to detect the stimulatory effect of DCs on T cell proliferation and ELISA to determine IL-12p70 amount. Results Comparing with Sham group， the expression of P-selectin was up-regulated among tubulointerstitium mainly on renal tubular epithelial cell after unilateral ureteral obstruction on day 1， while CD1a+CD80+DCs being also found in renal interstitium. The expression of P-selectin and CD1a+CD80+DCs was increased evidently on day 7， and correlated with the degree of renal tubulointerstitial fibrosis closely. However， these changes became less conspicuous in rat treated with PsL-EGFmAb. In vitro experiment showed on day 5 after cultured with the induction of TNF-α， immature DCs highly expressed C-type lectin DC-SIGN of pattern recognition receptors； the expression of co-stimulatory molecules such as CD11c，CD83，CD80 and CD86 on mature DCs was up-regulated in paralleling with the mRNA level of NF-κB；the secretion of IL-12 was enhanced， as well as displaying the features of antigen-presenting cells with a higher ability to induce proliferation of T lymphocytes in vitro. In addition， L-selectin expressed highly on immature DCs， but lowly on mature DCs， neither of two DCs expressed P- and E-selectin. Compared with the IL-10 treated group， PsL-EGFmAb had an inhibitory effect on DC-SIGN of DCs with down-regulating the mRNA level of NF-κB. PsL-EGFmAb could also inhibited CD11c， CD83， CD80， CD86 expression， reduced secretion of IL-12， and inhibited T cell proliferation stimulated by DCs in vitro. Conclusion DCs may play a critical role on initiating the inflammatory injury of renal tubulointerstitium， and the inhibitory effect of PsL-EGFmAb on DC maturation and function correlated with the inhibition of DC-SIGN， which is mainly mediated through NF-κB signaling pathway.

Objective To investigate the role of overexpression of Smad7， the inhibitory factor of TGF-β/Smads signaling，in epithelial-mesenchymal transition(EMT) of peritoneal mesothelial cells. Methods Peritoneal fibrosis rat model was built by daily intraperitoneal injection with 4.25% Dineal (100 ml/kg) and lipopolysaccharide(LPS)(0.6 mg/kg) at day 8， 10， 12， 22， 24， 26. Smad7 or control empty vectors was transferred at day 0，14 and was induced by doxycline in the daily drinking water(200 mg/L). Rats were sacrificed on day 28 and the expression of TGF-beta/Smads， α-SMA and E-cadherin was examined. Results Compared with normal rats， empty vector rats showed higher expression of phosphorylated Smad2/3. α-SMA expression was elevated but E-cadherin was reduced. Under electron microscope，the mesothelial cells removed to submesothelial zone and showed large bundles of actin microfilaments and dense bodies within the cytoplasm. Basement membrane was broken. After induction of Smad7 in peritoneal fibrosis rats， the morphology of mesothelial cells normalized partly， phosphorylated Smad2/3 was reduced. Moreover， expression of E-cadherin was increased， expression of α-SMA was dramatically reduced. Conclusion Inhibition of TGF-β/Smad signaling by Smad7 overexpression may inhibit the epithelial-mesenchymal transition of mesothelial cell， which may provide a new therapeutic method for peritoneal fibrosis by overexpression of Smad7.

Objective To study the effect of injured podocytes on glomerular maturation and its underlying mechanism in neonatal mice. Methods Single i.p.injection with puromycin aminonucleoside (PA， 0.1 mg/g BW) was given to ICR neonatal mice at day 1 after birth (1 dpp). Littermates injected with normal saline (NS) were used as control. Animals were examined for urine protein， blood pressure， kidney weight/body weight (KW/BW)， renal histology at 2， 4， 8， 12， 30， 60 and 90 dpp (n=6~9 for each group). Immunohistochemistry and quantitative RT-PCR were performed to examine the expression of WT-1， CD31， VEGF， Flk-1， Ang-1， Ang-2， Tie-1 and Tie-2. Results Mice with PA injection had lower kidney weight and body weight at all time points as well as lower KW/BW at 4， 8， 12 dpp when compared with NS controls. Electron microscopy revealed nearly complete foot process effacement and segmental microvillous transformation as early as 1 day after PA injection. PA-injected kidneys showed fewer capillary loops and decreased maturation index as well as less CD31-positive endothelium in cortical glomeruli at 12 dpp. Glomerular mesangial injury and developing glomerulosclerosis along with proteinuria were noted in PA-injected kidneys starting from 30 dpp. Significantly increased systolic blood pressure was detected at 60 dpp in PA mice. Compared with NS injection， PA injection significantly induced decreased mRNA expression of Flk-1 and Tie-2 as well as increased expression of Ang-1，without obvious changes of VEGF at 2 dpp. Conclusions Podocytes in neonatal kidney of ICR mice are susceptible to PA. Such podocyte injury can alter the expression of VEGF and angiopoietin system in glomeruli， leading to abnormal development of glomerular capillaries， and subsequent proteinuria， hypertension and glomerulosclerosis.

Objective To observe the role of rosiglitazone in unclipped kidneys of two-kidney- one-clip hypertensive rats and examine its relationship to angiotensin Ⅱ receptors. Methods Two-kidney-one-clip hypertensive rats were divided randomly into 4 groups as follows: positive control group (CONT)， traditional antihypertensive drugs group (TAHD， reserpine 50 µg·kg^-1·d^-1， dihydralazine 6.25 mg·kg^-1·d^-1 and hydrochlorothiazide 6.25 mg·kg^-1·d^-1， regular-dose rosiglitazone group (RRGL， rosiglitazone 5 mg·kg^-1·d^-1)， and high-dose rosiglitazone group (HRGL， rosiglitazone 20 mg·kg^-1·d^-1). Sham operation rats were as negative controls. Each group had 8 rats. Animals were monitored and sacrificed at 10th week. Results Blood systolic pressure in TAHD group and HRGL group was significantly lower than that in CONT group [TAHD(137±27 ) mm Hg and HRGL(143±16) mm Hg vs CONT (191±25) mm Hg， P < 0.05]， but no significant difference between the former two groups was found. Nor did the blood systolic pressure between RRGL group [(176±18) mm Hg] and CONT group. At 10th week， rats in SHAM group and treated groups had lower urinary urinary protein excretion rate， glomerular injury score and wall-to-lumen ratio of arteriole than those in CONT group[vs CONT urinary protein excretion rate (44.60±17.40) mg/24 h， P < 0.05； vs CONT glomerular injury score 60.85±33.05， P < 0.05； vs CONT wall-to-lumen ratio of arteriole 2.33±1.01， P < 0.01，except TAHD group]. Though with the similar level of blood pressure， blood glucose and lipid， HRGL， compared with TAHD group showed lower urinary protein excretion rate [HRGL (16.78±3.50) mg/24 h vs TAHD (27.94±12.79) mg/24 h， P < 0.05]， decreased glomerular injury score (HRGL 18.04±7.76 vs TAHD 27.92±6.39， P < 0.05) and wall-to-lumen ratio of arteriole (HRGL 1.75±0.38 vs TAHD 2.16±0.90， P < 0.05) in the cortexes of unclipped right kidneys. The expression of type 1 angiotensin Ⅱ receptor (AT1R) mRNA was no difference in HRGL group and TAHD group， but the expression of type 2 angiotensin Ⅱ receptor (AT2R) mRNA was more intensive in HRGL group. Conclusion Rosiglitazone can protect the kidneys from hypertensive injury， especially in high dose. The beneficial effects seem incompletely dependent on the metabolism modulating and reduction of blood pressure， but in relationship to the upregulation of AT2R mRNA.

Objective To investigate the effect of 12-lipoxygenase(12-LO) on the angiotensin Ⅱ type 1 receptor(AT1R) expression in mesangial cells (MC). Methods p38 MAPK activation and ECM protein expression were determined using AngⅡ-stimulated MC derived from normal and 12-LO knockout mice. AT1R expression was determined using 12-LO product 12(S)-HETE-stimulated MC， MC transfected with 12-LO gene and microdissected glomeruli derived from 12-LO knockout mice. RT-PCR and Western blot were used for evaluating mRNA and protein expression respectively. Results AngⅡ stimulation increased p38 MAPK activation and ECM protein expression in normal MC， but not in MC derived from 12-LO knockout mice. Time-dependent and dose-dependent experiment showed that 12(S)-HETE increased AT1R protein′expression in MC. Similarly， 12(S)-HETE increased AT1R mRNA expression in MC compared with control MC(P < 0.01). Furthermore， AT1R expression was lower in glomeruli derived from 12-LO knockout mice relative to genetic controls(P < 0.01) and MC stably overexpressing 12-LO had greater AT1R protein and mRNA expression relative to control MC(P < 0.01). Conclusion 12-LO activation can upregulate AT1R expression in MC.

Objective To initially investigate the mechanism of COX-2 inhibitor inducing cell apoptosis through the observation of celecoxib(CXB)， a specific COX-2 inhibitor，inducing apoptosis of cyst lining epithelial cells of human polycystic kidney. Methods (1)Primarily cultured cell was divided into control group and CXB group to evaluate the proliferative state by Brdu assay.(2)The cell apoptosis was observed by transmitted electronic microscope after being cultured in CXB 2×10^-5 mol/L for 24，48 hours.(3)The cell apoptosis and apoptotic rate were detected by TUNEL assay.(4)The cell apoptotic rate were measured by AnnexinV， PI-labeled flow cytometry after being cultured in CXB 2×10^-5 mol/L for 0， 24， 48 hours.(5)Protein expression of Bax，Bcl-2，caspase 3 was examined by Western blotting. Results (1)The Brdu assay revealed that CXB inhibited cell growth in a concentration-dependent manner， with the maximum growth inhibition ratio of 63.9% when treated by CXB 2×10^-5 mol/L for 24 h.(2)Typical morphological changes of apoptotic cell were apoptotic body， nuclear concentration，chromatin aggregation， endochylema vacuolization and ravinement under eletrou microscope. (3)TUNEL assay showed that the apoptotic rate was (2.8±0.2)% in control group， and (28.5±1.6)%， (48.5±1.2)% in CXB group for 24，48 hours respectively，with significant differences to control group(P < 0.05). (4) AnnexinV， PI-labeled flow cytometry showed that，in 0，0.5，1，2×10^-5 mol/L CXB group，the apoptotic rates were(3.15±0.05)%，(7.15±0.11)%，(7.76±0.08)%，(12.15±0.07)% for 24 hours respectively，and(13.53±0.21)%，(18.36±0.17)%，(24.87±0.25)%，(53.66±0.32)% for 48 hours respectively. Significant differences were found among corresponding groups(all P < 0.01). (5) Extracted total cell protein in every group and more protein of Bax，Bcl-2 expressed in CXB-treated group was detected by Western blotting than that in control group.Conclusions CXB can inhibit the proliferation of cyst liner epithelial cells in a time- and concentration-dependent manner， and induce cell apoptosis through increasing the ratio of Bax/Bcl-2. CXB is hopeful to become an effective drug to treat ADPKD.