姜黄素抗顺铂肾毒性作用及其机制研究

Study on the Protective Effect and Mechanism of Curcumin on Cisplatin-induced Nephrotoxicity

目的探讨姜黄素(CMN)抗顺铂所致大鼠肾损害的作用及其机制。方法选择48只雄性Wistar大鼠,随机分为Ⅰ(n=12),Ⅱ(n=6),Ⅲ(n=6),Ⅳ(n=12),Ⅴ(n=12)组,分别行第1次腹腔注射:生理盐水(Ⅰ,Ⅱ,Ⅲ组)、CMN 30 mg/kg(Ⅳ组)、CMN30 mg/kg+锌原卟啉Ⅸ(ZnPPⅨ)10 mg/kg(Ⅴ组),8 h后,从Ⅰ,Ⅳ,Ⅴ组中各任选6只鼠处死,检测HO-1蛋白表达与活力。余鼠再行第2次腹腔注射:生理盐水(Ⅰ组),CMN 20 mg/kg+顺铂6 mg/kg(Ⅱ组)。顺铂6 mg/kg(Ⅱ,Ⅳ,Ⅴ组),5 d后处死,检测血肌酐(Cr)、尿素氮(BUN)、肾脏系数、肾组织超氧化物歧化酶(SOD)活力及谷胱甘肽(GSH)和丙二醛(MDA)含量。结果顺铂可明显升高肾组织氧化应激水平并严重损伤肾脏的结构和功能,姜黄素仅有较弱的直接抗顺铂肾毒性作用,但用姜黄素预处理上调HO-1蛋白表达及活力能显著增强其抗顺铂肾毒性作用;反之,用ZnPPⅨ抑制HO-1活力则可消除姜黄素抗顺铂肾毒性作用。结论姜黄素主要通过上调HO-1蛋白表达有效拮抗顺铂所致的氧化应激性肾损伤。

Objective To investigate the protective effects of eureumin（CMN） on eisplatin-indueed nephrotoxieity in rats and the possible mechanisms. Methods 48 male wistar rats were randomly divided into 5 groups ： groupⅠ （ n = 12 ）, groupⅡ （ n = 6 ）, group Ⅲ（ n = 6）, groupⅣ （ n = 12 ）, groupV （ n = 12 ）. Rats received intraperitoneally injection for the first time respectively with saline （groupⅠ, groupⅡ, groupⅢ）, CMN 30 mg/kg （groupⅣ）, CMN 30 mg/kg ＋ Zinc protoporphyrin IX （ZnPPⅨ） 10 mg/kg （groupV）. 8 hours later, half rats in groupⅠ, groupⅣ, groupⅤ were killed to analyse renal HO-1 protein express and activity. Other rats reeeived the intraparitoneally injection for the second time respectively with saline （groupⅠ）, Cisplatin 6mg/kg ＋ CMN 30mg/ kg（groupⅢ） and eisplatin 6 mg/kg（ groupⅡ, groupⅣ, groupV）. 5 days later, all the animals were killed to measure the blood ereatinin（Cr） , urea nitrogen（BUN） and analyse the renal superoxide dismutase （SOD） activity, glulathion （GSH） and malondialdehyde（MDA） content and histopathological lesion. Results Cisplatin could increase the renal oxidative stress level and damage seriously the renal histology construction and function. CMN only has slight direct protective effect against the cisplatin - induced nephrotoxicity. But the renal protective effect would increased significantly by pretreatment with CMN to up-regulate renal HO-1 protein level and considerably attenuated by inhibiting HO-1 protein activity with ZnPPIX. Conclusion CMN can protect against cisplatin-induced oxidative stress renal injury by inducing HO-1.