表没食子儿茶素-3-没食子酸酯缓解顺铂所致大鼠急性肾损伤效果评价

doi:10.16431/j.cnki.1671-7236.2023.12.039

摘要/Abstract

摘要： 【目的】评价不同浓度表没食子儿茶素-3-没食子酸酯(EGCG)对顺铂所致大鼠急性肾损伤的保护效果,筛选出EGCG缓解顺铂肾毒性的最佳浓度。【方法】将30只Wistar大鼠随机分为5组(6只/组):正常对照组(CON)、顺铂组(CIS)、低剂量EGCG(20 mg/kg)＋顺铂组(LCE)、中剂量EGCG(40 mg/kg)＋顺铂组(MCE)及高剂量EGCG(80 mg/kg)＋顺铂组(HCE)。CON和CIS组大鼠持续28 d灌胃生理盐水(40 mg/kg),CIS组在第26天腹腔注射CIS(7 mg/kg);LCE、MCE和HCE组大鼠持续28 d灌胃相应剂量的EGCG,在第26天腹腔注射CIS,第29天采集大鼠血清和肾脏组织。检测药物灌服期间大鼠生理和生化指标变化,病理学检测各组大鼠肾脏组织病理变化,初步评价EGCG在CIS所致大鼠急性肾损伤中保护作用,筛选出EGCG最佳有效浓度;Western blotting检测凋亡蛋白Bax、Bcl-2、Caspase-3及炎症因子白细胞介素-6(IL-6)和IL-10蛋白表达变化,进一步证实EGCG的保护效果。【结果】与CON组相比,CIS组大鼠采食量、饮水量和体重在第28天显著下降(P＜0.05),血清中尿素氮(BUN)与肌酐(CRE)含量显著上升(P＜0.05),肾小管扩张明显,有蛋白管型,肾损伤严重;与CIS组相比,MCE组大鼠采食量、饮水量和体重显著上升(P＜0.05),血清中BUN、CRE含量显著下降(P＜0.05),MCE组肾脏肾小管扩张程度得到明显改善,LCE和HCE组无明显变化。因此,选用40 mg/kg EGCG用于后续试验。Western blotting检测结果表明,与CON组相比,CIS组Bax、IL-6、Caspase-3蛋白表达量显著上升(P＜0.05),Bcl-2、IL-10蛋白表达量显著下降(P＜0.05);与CIS组相比,MCE组Bax、IL-6、Caspase-3蛋白表达量显著下降(P＜0.05),Bcl-2、IL-10蛋白表达量显著升高(P＜0.05)。【结论】EGCG对CIS诱导的大鼠急性肾损伤具有保护作用,以40 mg/kg为最佳,其保护机制与抑制肾细胞凋亡和炎症相关。

关键词: 表没食子儿茶素-3-没食子酸酯(EGCG); 顺铂; 大鼠; 急性肾损伤

Abstract: 【Objective】 This study was aimed to evaluate the protective effects of different concentrations of epigallocatechin gallate (EGCG) on cisplatin-induced acute kidney injury in rats,and to select the best concentration of EGCG to alleviate cisplatin nephrotoxicity.【Method】 Thirty Wistar rats were randomly divided into 5 groups:Normal control group (CON),cisplatin group (CIS),low dose (20 mg/kg) EGCG＋cisplatin group (LCE),medium dose (40 mg/kg) EGCG＋cisplatin group (CE) and high dose (80 mg/kg) EGCG＋cisplatin group (HCE).Rats in CON group and CIS group were perfused with normal saline (40 mg/kg) for 28 days,and CIS group was intraperitoneally injected with CIS (7 mg/kg) on the 26th day.Rats in LCE,MCE and HCE groups were given corresponding dose of EGCG for 28 days,CIS was injected intraperitoneally on the 26th day,and serum and kidney tissues were taken on the 29th day.Firstly,the changes of physiological and biochemical indexes of rats were detected during drug administration,then the pathological changes of kidney tissue of rats in each group were detected,the protective effect of EGCG on acute kidney injury induced by CIS was preliminarily evaluated,and the best effective concentration of EGCG was selected.Then the protein expression changes of apoptosis (Bax, Bcl-2 and Caspase-3) and inflammation (IL-6 and IL-10) were detected by Western blotting to further confirm the protective effect of EGCG.【Result】 Compared with CON group,the diet,drinking water and body weight of rats in CIS group decreased significantly on the 28th day,while urea nitrogen (BUN) and creatinine (CRE) increased significantly (P＜0.05).The renal tubules were obviously dilated,with protein cast,and the renal injury was serious.Compared with CIS group,the diet,water consumption and weight of rats in MCE group were increased significantly (P＜0.05),and the contents of BUN and CRE in serum were decreased significantly (P＜0.05).The renal tubular dilatation in MCE group was significantly improved,but there was no significant change in LCE and HCE groups.Therefore,40 mg/kg EGCG was selected for the follow-up experiment.Western blotting result showed that compared with CON group,the expressions of Bax,IL-6 and Caspase-3 in CIS group were increased significantly (P＜0.05),while the expressions of Bcl-2 and IL-10 decreased significantly (P＜0.05).Compared with CIS group,the expressions of Bax,IL-6 and Caspase-3 in MCE group were decreased significantly (P＜0.05),while the expressions of Bcl-2 and IL-10 were increased significantly (P＜0.05).【Conclusion】 EGCG had a protective effect on CIS-induced acute kidney injury in rats (40 mg/kg was the best),which was related to the inhibition of renal cell apoptosis and inflammation.

Key words: epigallocatechin gallate (EGCG); cisplatin; rat; acute kidney injury

中图分类号:

S854.5^＋3

汪星萍, 曹家慧, 苟丹丹, 邵义文, 迟士鹏, 杨春雪, 徐恩爽. 表没食子儿茶素-3-没食子酸酯缓解顺铂所致大鼠急性肾损伤效果评价[J]. 中国畜牧兽医, 2023, 50(12): 5186-5193.

WANG Xingping, CAO Jiahui, GOU Dandan, SHAO Yiwen, CHI Shipeng, YANG Chunxue, XU Enshuang. Effect of Epigallocatechin Gallate on Alleviating Acute Kidney Injury Induced by Cisplatin in Rats[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(12): 5186-5193.

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