Effect of sinomenine on apoptosis in renal tubular epithelial cells of rats subjected to renal ischemia-reperfusion: the relationship with JNK signaling pathway

Objective To evaluate the effect of sinomenine on apoptosis in renal tubular epithelial cells of rats subjected to renal ischemia-reperfusion(I/R), and the relationship with C-Jun N-terminal kinase(JNK)signaling pathway. Methods Fifty-four male Wistar rats, aged 6-8 weeks, weighing 180-220 g, were randomly divided into 3 groups(n=18 each)using a random number table: sham operation group(group S), I/R group and sinomenine group(group SIN). Renal ischemia was induced by occlusion of the left renal pedicle for 45 min followed by reperfusion, and the right kidney was removed immediately after onset of reperfusion in anesthetized rats in I/R and SIN groups.In group SIN, sinomenine 60 mg/kg was injected intraperitoneally at 30 min before reperfusion, while the equal volume of normal saline was given instead of sinomenine at the same time point in S and I/R groups.Six animals in each group were selected at 0.5, 6 and 24 h of reperfusion, blood samples were collected by cardiac puncture for determination of serum creatinine(Cr)and blood urea nitrogen(BUN)concentrations.Immediately after blood sampling, the left kidney was removed for examination of pathological changes in renal tissues(with light microscopes)and for determination of phosphorylated JNK(p-JNK)and caspase-3 expression(by immune-histochemistry)and apoptosis in renal tubular epithelial cells(by TUNEL). The apoptotic rate was calculated. Results Compared with group S, the serum Cr and BUN concentrations were significantly increased, the expression of p-JNK and caspase-3 was up-regulated, and the apoptotic rate was increased in I/R and SIN groups.Compared with group I/R, the serum Cr and BUN concentrations were significantly decreased, the expression of p-JNK and caspase-3 was down-regulated, and the apoptotic rate was decreased in group SIN.The microscopic examination showed that the pathological changes of kidney were significantly attenuated in group SIN compared with group I/R. Conclusion The mechanism by which sinomenine attenuates renal I/R injury is related to inhibited activation of p-JNK signaling pathway and reduced apoptosis in renal tubular epithelial cells of rats. Key words: Sinomenium; Reperfusion injury; Kidney; Apoptosis; Kidney tubules; Epithelial cells; JNK mitogen-activated protein kinases