表没食子儿茶素没食子酸酯对顺铂诱导大鼠肾损伤的改善作用

摘要

AIM To investigate the improving effects of epigallocatechin gallate (EGCG) on rat kidney injury induced by cisplatin and its mechanism of action.METHODS Fifty male SD rats (10 rats/group) were randomly divided into blank control group,kidney injury group,EGCG low-,middle-and high-dose (25,50 and 100 mg/kg) groups.The kidney injury group and the drug administration group were treated with 7.5 mg/kg cisplatin by intraperitoneal injection to build the kidney injury model,and the blank control group was intraperitoneally injected with normal saline.After fourteen days of administration,the general condition and morphological changes of kidney tissue by HE staining were observed;BUN,Cr,Cys-c contents in serum,and IL-18,KIM-1 contents in urine were detected by ELISA;MDA,GSH and T-SOD contents in renal cortex were determined by kit;Western blot method was used to determine the contents of Nrf2 protein in renal contex cytoplasm and nucleus,and the expression level of HO-1 protein.RESULTS EGCG intervention could improve the pathological structural changes of rat kidney injury induced by cisplatin,decrease kidney index,and decrease serum Cr,Cys-c contents and urine IL-18,KIM-1 contents.Moreover,renal cortex MDA concentration decreased,and renal cortex GSH concentration,T-SOD activity increased.At the same time,renal cortex cytoplasm Nrf2 content reduced,but nucleus Nrf2 and total cell HO-1 contents increased.CONCLUSION EGCG plays a role in the improvement of rat kidney injury induced by cisplatin through the activation of Nrf2/HO-1 signal pathway.%目的 考察表没食子儿茶素没食子酸酯(EGCG)对顺铂诱导大鼠肾损伤的改善作用及其作用机制.方法 50只SD雄性大鼠(10只/组)随机分为空白对照组,肾损伤组,EGCG低、中、高剂量组(25、50、100 mg/kg).肾损伤组及给药组腹腔注射7.5 mg/kg顺铂制备肾损伤模型,空白对照组腹腔注射生理盐水.给药14d后,观察各组大鼠一般状况,HE染色法观察肾组织形态学变化;ELISA试剂盒法检测血清中尿素氮(BUN)、肌酐(Cr)、胱抑素C(Cys-c)的含有量和尿液中白介素-18 (IL-18)、肾损伤分子-1(KIM-1)的含有量;试剂盒法检测肾皮质中丙二醛(MDA)、抗氧化酶体系谷胱甘肽(GSH)、总超氧化物歧化酶(T-SOD)的含有量;Western blot法检测肾皮质胞浆、胞核中核因子2相关因子2(Nrf2)蛋白的含有量及血红素氧合酶1(HO-1)蛋白的表达水平.结果 EGCG干预可以改善顺铂诱导大鼠肾损伤病理结构改变,肾指数降低,血清中Cr、Cys-c含有量降低,尿液中IL-18、KIM-1含有量降低,肾皮质中MDA浓度降低,GSH浓度、T-SOD活性升高.同时,肾皮质中胞浆Nrf2含有量降低,胞核Nrf2、总细胞HO-1含有量升高.结论 EGCG可通过激活Nrf2/HO-1信号通路,发挥对顺铂诱导大鼠肾损伤的改善作用.