鞣花酸对顺铂引起小鼠急性肾损伤的影响

Effects of ellagic acid on cisplatin-induced acute kidney injury in mice

目的:研究鞣花酸(EA)对顺铂引起小鼠急性肾损伤的减轻作用,探讨其可能的机制.方法:将32只雄性昆明小鼠随机分为对照组、模型组、EA给药组(10,30mg/kg),给予顺铂(25mg/kg)建立小鼠急性肾损伤模型,观察EA给药后的改善作用.取小鼠血清并用试剂盒测定尿素氮(BUN)、肌酐(Cr)、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)和肾组织中总超氧化物歧化酶(T-SOD)、丙二醛(MDA)及还原型谷胱甘肽(GSH)水平.用HE和Tunel染色观察肾脏病理结构变化和细胞凋亡,用Western blotting测定肾组织中促凋亡蛋白(Bax)和抗凋亡蛋白(Bcl-2)的表达.结果:与模型组比较,EA均能不同程度地降低血清中BUN,SCr,MDA,TNF-α和IL-1β水平,增加肾组织中GSH和T-SOD的活性;下调肾组织中Bax,上调Bcl-2的蛋白表达水平;改善顺铂所致的病理变化.结论:EA对顺铂引起的肾损伤具有保护作用,这与EA的抗氧化、减少炎症反应和抑制肾小管上皮细胞凋亡有关.

Objective:To investigate the alleviation effect of ellagic acid(EA)on cisplatin-induced acute kidney injury in mice and to explore the possible mechanism.Methods:32 male Kunming mice were randomly divided into control group,model group,low and high dose groups(10,30 mg/kg EA).An acute kidney injury model was established by a single intraperitoneal injection of 25 mg/kg cisplatin to observe the improvement effect after EA administration.Serum urea nitrogen(BUN),creatinine(SCr),tumor necrosis factor alpha(TNF-α),interleukin-1β(IL-1β)and total superoxide dismutase(T-SOD),malondialdehyde(MDA),and glutathione(GSH)in renal tissues were detected in the serum of each group.Renal pathological changes and apoptosis were observed by HE and Tunel staining.The expressions of proapoptotic protein(Bax)and anti-apoptotic protein(Bcl-2)in renal tissues were determined by Western blotting.Result:Compared with the model group,EA could reduce the levels of BUN,SCr,MDA,TNF-αand IL-1βin serum,increase the activity of GSH and T-SOD in kidney tissue,and down-regulate Bax in kidney tissue and up-regulate Bcl-2 protein expression levels,also improve pathological changes induced by cisplatin.Conclusion:EA has a protective effect on cisplatin-induced renal injury,which may be associated with EA′s antioxidant,inflammatory response reduction and inhibition of renal tubular epithelial cell apoptosis.