Up-regulation of intermedin protects kidney from ischemia/reperfusion injury
ZHU Guo-zhen, LI Rong-shan, QIAO Xi, HUANG Xiao-guang, ZHANG Xiao-qin, WANG Chen, SHAO Shan, BAI Bo.
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Department of Nephrology, the Second Hospital, Shanxi Medical University, Taiyuan 030001, ChinaCorresponding author: LI Rong-shan, Email: rongshanli@yahoo.com.cn
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History+
Received
Revised
Published
1900-01-01
1900-01-01
2012-01-15
Issue Date
2012-01-15
Abstract
Objective To investigate the effect of intermedin (IMD) on renal ischemia/reperfusion(I/R) injury after the up-regulation of IMD. Methods A total of 24 healthy Wistar male rats were randomly divided into four groups, sham-operated group, I/R group, IMD gene transfection +I/R group and empty plamid +I/R group. All the animals were killed at the end of 24 h of reperfusion. Histological changes and renal function were estimated. The expression and site of IMD were determined by Immunohistochemistry method, semi-quantitative RT-PCR and Western blotting. The protein expressions of endothelin 1 (ET-1), tumor necrosis factor α (TNF-α) were detected by Western blotting. Results Compared with sham-operated group, tubulointerstitial pathological injury was significant aggravated in I/R group (7.6±2.3) and empty plamid +I/R group(7.0±1.8), and such injury was improved in IMD+I/R group (1.5±0.8) (P<0.05). Compared with I/R group and empty plamid +I/R group, the renal dysfunction of IMD +I/R group was obviously lessened [BUN:(7.73±1.03) mmol/L vs (10.13±2.14) mmol/L, (9.77±1.92) mmol/L; Scr: (58.50±3.27) μmol/L vs (80.33±7.15) μmol/L, (75.67±7.58) μmol/L, all P<0.05]. IMD expression was weak in the plasma of tubulointerstitial cells in sham-operated group, and was up-regulated in I/R group. Compared with I/R group, immunohistochemical IMD expression increased obviously (262.03±67.89 vs 175.57±48.06, P<0.01). The mRNA expression of IMD in IMD+I/R group was up-regulated significantly by 60.7% , 66.1% and the protein expression of IMD in IMD+I/R group increased significantly by 51.4%, 55.9% as compared to I/R and empty plasmid +I/R group. Meanwhile, the protein expressions of ET-1 and TNF-α in IMD+I/R group were obviously lower compared with those in I/R group (ET-1: 0.08±0.02 vs 0.17±0.02; TNF-α: 0.21±0.04 vs 0.35±0.02, all P<0.05). Conclusion IMD gene transfected into kidneys of rats prior to I/R surgery can attenuate the over-expressions of both ET-1 and TNF-α in I/R injured rat kidneys as well as the damages to the structure and function of the kidneys.