Effects Of Simvastatin On The Expressions Of Wnt/JNK In Rats With Renal Ischemia-Reperfusion Injury

Objective: Effect of simvastatin on the expression of Wnt/JNK in rats with renalischemia reperfusion injury.Methods:36male Wistar rats were divided randomly into sham operation group,ischemia reperfusion group and simvastatin treated group, for each including two phases at6hour and48hour. Rats in sham operation group had renal arteries separated withoutclipping.IRI model was established by bilateral clipping of renal arteries for45minute. Rats insimvastatin treated group had administered simvastatin20mg kg^-1d^-1for seven days beforeoperation. The levels of serum creatinine （Scr） were detected at6hour and48hour time points.The renal pathological changes were detected under light microscope. Immunohistochemistrywere used to detect expression levels of Wnt4, JNK1and TNFα which was the inflammatoryfactor of its signal path. The expression of Wnt4mRNA and JNK1mRNA were detected by realtime PCR.Results:1. Scr detect: Compared with the sham operation group, the levels of Scr was increasedsignificantly in ischemia reperfusion group, and the levels of Scr was decreased in simvastatintreated group （P0.01）. It was obvious at6hour（P0.01）.2. Renal pathological change: The pathomorphological changes of renal tissues insham operation group were normal observed by light microscopes. Histopathological changes ofrenal tubular epithelial cells were swelling, desquamative or flattened epithelia, necrotic debris,edema in the interstitium and inflammatory cell infiltration in ischemia reperfusion group. It isobvious at6hour. Pathological changes in kidney were milder in simvastatin treated group.3. Wnt4, JNK1and TNFα display: The expression of Wnt4, JNK1and TNFα protein andthe content of wnt4mRNA and JNK1mRNA in renal tubular epithelial cells were increasedsignificantly in the ischemia reperfusion group than those in the sham operation group（P0.01）.It was obvious at6hour（P0.01）. The expression was relieved in simvastatin treated group （P0.05）.4. Correlation analysis: The expression of JNK1was positive correlation with theexpression of Wnt4and TNFα r_s=0.93,r_s=0.92. The content of wnt4mRNA was positivecorrelation with the JNK1mRNA r_s=0.68.And those were positive correlation with the levelsof Scr r_s=0.76, r_s=0.72,r_s=0.72, r_s=0.70, r_s=0.35.Conclusion: 1. The expression of Wnt4, JNK1and TNFα and the content of wnt4mRNA and JNK1mRNA were gradually up regulated after renal IRI. The expression of JNK1was positivecorrelation with the expression of Wnt4and TNFα, the same as the content of wnt4mRNA andthe JNK1mRNA. Above all were positive correlation with the levels of Scr, which indicatedWnt/JNK signal pathway activated TNFα that induces inflammatory reaction.2. Simvastatin pretreatment protects kidney against ischemia after renal ischemiareperfusion injury by Wnt/JNK signal pathway, relieving the renal function and theorganizational structure damage.