Objective    To analyze the significance of global end-diastolic volume index (GEDVI) in acute kidney injury (AKI) after septic shock.    Methods    A retrospective analysis of 61 patients was performed. The patients were diagnosed of septic shock in emergency ward of Shenyang Military Hospital from 2012 March to 2013 May and were monitored by pulse indicator continuous cardiac output (PiCCO) . The patients were divided into two groups: low GEDVI group (GEDVI＜700 ml/m2, 29 cases) and high GEDVI group (GEDVI≥700 ml/m2, 32 cases) by evaluating GEDVI of 24 hour after PiCCO. Several physiologic and biochemical indexes were recorded, including the hemodynamic parameters at the beginning and the 24 h of PiCCO monitoring, Scr, BUN, lactic acid, incidence and mortality of AKI, baseline glomerular filtration rate, baseline Scr, APACHE Ⅱ scores, mortality during the period of emergency ward or within 28 d after the diagnosis.    Results    A total of 26 cases in high GEDVI group (81.3%) were attacked with AKI, while 16 cases in low GEDVI group (55.2%) were attacked with AKI, the incidence of AKI in high GEDVI group was significantly higher than that in the low GEDVI group. A COX regression analysis of mortality was performed between the patients staying at emergency ward and during 28 d after diagnosis. The results indicated that AKI and GEDVI had no relation with patients’ death. Therefore, AKI and GEDVI could not be considered as the risk factors for the prognosis.    Conclusions    High GEDVI can significantly increase the incidence of AKI after septic shock, therefore high GEDVI should be avoided as much as possible in the course of clinical treatment.

Objective    To explore the association between polymorphisms in non-muscle myosin heavy chain 9 gene (MYH9) and hypertension susceptibility in chronic kidney disease (CKD) patients.    Methods    Five hundred and ninety-five persons, including 301 patients with CKD and 294 healthy controls, were enrolled in the study. Two single nucleotide polymorphisms (SNPs) (rs3752462, rs4821480) were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study. The discrepancies of the patients'quantitive traits (including age, sex, systolic and diastolic blood pressure, frequency of different primary diseases and using different kinds of antihypertensive drugs) among different genotypes of the two MYH9 SNPs were analyzed. Meanwhile, the association between polymorphisms in MYH9 and hypertension susceptibility in CKD patients were analyzed in the rs3752462 site.    Results    The systolic blood pressure of CT genotype patients[(147.94±27.40) mm Hg] was significantly higher than that of CC genotype patients [(136.43±19.09) mm Hg] by single factor analysis of variance (P＜0.05). The frequency of using all kinds of antihypertensive drugs for CC genotype patients (7.4%) was lower than that of TT (43.9%) and CT (48.7%) genotype patients (P＜0.05). After correcting the age factor, the result of Logistic regression analysis showed that CC genotype was a protective factor of systolic blood pressure increasing. The probability of high blood pressure for CT genotype patients with CKD was 0.175 times than that of CC genotype (95% CI 0.071,0.431).    Conclusions    The CKD patients who carry the rs3752462 site CC genotype of MYH9 gene are not prone to high blood pressure. Polymorphism of MYH9 gene rs3752462 site is associated with systolic blood pressure in CKD patients. It may indicate that allele C mutation for T can lead to the increase in systolic blood pressure.

Objective    To reveal the role of inhibitor of nuclear factor kappa B kinase alpha(IKKα) in renal inflammation after renal ischemia-reperfusion （IR） injury and its potential associated mechanism.    Methods    Ischemia-reperfusion injury models were induced in a total of 24 healthy C57BL/6 male mice. Renal function and histological changes were estimated. The expression and site of IKKα, p52, RelB, IL-10 and IL-18 were determined by immunohistochemistry and Western blotting. After the short hairpin RNA(shRNA)targeting IKKα was injected into renal parenchyma, renal function and protein expressions of IKKα, p52, RelB, IL-10, IL-18 were detected.    Results    Compared with sham-operated group[Scr(7.30±0.13) μmol/L, BUN (8.39±0.30) mmol/L], levels of Scr [(29.80±2.10) μmol/L, (27.00±3.40) μmol/L, (23.00±3.70) μmol/L] and BUN [(9.47±3.50) mmol/L, (11.68±4.30) mmol/L, (13.12±2.10) mmol/L] were higher on day 1, 3, 7 and the injury of kidney was serious in IR injury group. Immunohistochemical expression of both IL-18 and IL-10 were increased. Markedly increased IKKα, p52 and RelB protein expression were noted in experiments from day 1 to day 7 during kidney recovery period, with a peak on day 3 and then decreasing toward baseline after day 7. Compared with IR injury group, low-expression of IKKα by injection of shRNA up-regulated the expression of IL-18 and down-regulated the expression of IKKα, p52, RelB and IL-10.    Conclusions    The NF-κB pathway is activated and IKKα expression is up-regulated during the kidney ischemia-reperfusion injury, low-expression of IKKα may block inflammation resolution via down-regulation of alternative NF-κB pathway family members of both p52 and RelB.

Objective    To investigate the effects of p-cresol on human umbilical vein endothelial cells.    Methods    The effects of p-cresol on endothelial cell growth, cell cycle, cell morphological change and p21 protein were detected by the CCK-8 assay, flow cytometry assay, inverted microscope and Western blotting.    Results    P-cresol could inhibit the growth of human umbilical vein endothelial cells in dose- and time-dependent manners (all P＜0.05). The human umbilical vein endothelial cells treated with p-cresol became elongated processes, cloudy cytoplasm, and irregular shapes. The p-cresol stopped human umbilical vein endothelial cells at cell cycle G1 and had no effect on cell apoptosis. The p-cresol could increase protein expression of p21 in a dose dependent manner (P＜0.05).    Conclusion    P-cresol can increase protein expression of p21, induce cell cycle arrest at G1 stage and inhibit the proliferation of human umbilical vein endothelial cells.

Objective    To evaluate the expression of type III sodium-dependent phosphate cotransporter (Pit-1) in cardiac damages in uremic rats fed with high phosphate diet.    Methods    Male SD rats were given an adenine and high phosphate diet as uremic rats (n＝18, uremic rats) or just high phosphate diet (NHP group, n＝6). After making uremic models, 18 rats were randomly divided into three groups as follow: uremic rats received high phosphate diet only (UHP group, n＝6); uremic rats received high phosphate diet and intraperitoneal phosphonoformic acid (PFA) 0.15 g·kg-1·d-1 (UHP＋PFA group, n＝6 ); uremic rats received high phosphates diet and intraperitoneal normal saline 0.15 g·kg-1·d-1 (UHP＋NS group, n＝6). At the end of 4th week and 8th week, serum Scr, Ca, P, and urine Ca, P were examined. At the end of the 8th week, the rats were sacrificed, and left ventricle weight, myocyte diameter, cardiac fibrosis were measured. The expression of PiT-1, TGF-β1, Cbfα-1, phosphorylation p38 mitogen-activated protein kinase (p-p38MAPK) and ERK (p-ERK) were determined by Western blotting.    Results    At the end of 4th week, Scr was higher in the uremic rats than that in the NHP rats. There was no significant difference of serum Ca, P, 24 h urinary P and Ca clearance among 4 groups (P＞0.05). At the end of 8th week, serum P was higher and Ca was lower in uremic groups than that in NHP group (P＜0.05). There was no significant difference of Scr, serum Ca, P, 24 h urinary P and Ca clearance among uremic groups (P＞0.05). Compared with those in NHP rats, the left ventricle weight, myocyte diameter, and the collagen volume fraction (%) increased in UHP group and UHP＋NS group (all P＜0.05), however, these parameters were ameliorated in UHP＋PFA group significantly (all P＜0.05). Western blotting showed that the expressions of PiT-1, TGF-β1, Cbfα-1,  p-p38MAPK and p-ERK were higher in UHP group and UHP＋NS group than that in NHP group and they decreased significantly in UHP＋PFA group (all P＜0.05).    Conclusions    There are significant cardiac damages in uremic rats received high phosphate diet, companied with increased PiT-1, TGF-β1, Cbfα-1, p-p38MAPK, p-ERK expressions. The adverse effects are ameliorated by PiT-1 blocker, indicating that PiT-1 play a role in high phosphate diet induced cardiac damages in uremic rats.

Objective    To investigate the expression of 4-hydroxynonenal (4-HNE) in the kidney of diabetic rats and the effect of probucol.    Methods    The rats were being intraperitoneal injected with STZ (60 mg/kg) to establish diabetic models. Then diabetic rats were randomly divided into diabetic group (group D, n＝24), probucol treated group (group P, n＝24). Normal rats were taken as control group (group C, n＝24). Rats in group P were treated by probucol (110 mg·kg-1·d-1); rats in group D and group C were given equal volume water instead. Scr, BUN, triglyceride (TG), total cholesterol (TC) and 24-hour urinary proteinin were measured at the 4th, 8th and 12th week. PAS staining and HE staining were used to evaluate the pathological changes of the kidney. The immunohistochemistry and Western blotting were used to detect the expression of 4-HNE in renal tissue.    Results    Levels of Scr, BUN, TG, TC and 24-hour urinary protein in group D were higher than those in group C at the 4th, 8th and 12th week(all P＜0.05); Levels of Scr, BUN, TG, TC and 24-huor urinary protein in group P were lower than those in group D at 4th, 8th and 12th week (all P＜0.05). The pathological changes of the kidney in group D were more serious than that in group P. The expression of 4-HNE in group D were higher than group C at the 4th, 8th and 12th week (all P＜0.05); The expression of 4-HNE in the kidneys of group P decreased significantly compared to that of group D at the same time (P＜0.05).    Conclusions    As an indicator of lipid peroxidation, the expression of 4-HNE significantly increases in the kidney of diabetic rat. Probucol may protect the diabetic kidney through decreasing the expression of 4-HNE and the level of lipid peroxidation.