维生素E抑制氯化汞诱导大鼠肾间质纤维化的抗氧化作用机制(英文)  

Effects of vitamin E on mercuric chloride-induced renal interstitial fibrosis in rats and the antioxidative mechanism

作　　者：陶艳艳[1] 王清兰[1] 袁继丽[1] 沈丽[1] 刘成海[1,2,3,4] 

机构地区：[1]上海中医药大学曙光医院肝病研究所,上海201203 [2]上海中医药大学肝肾疾病病证教育部重点实验室,上海201203 [3]上海中医药大学上海高校中医内科学E-研究院,上海201203 [4]上海市中医临床重点实验室,上海201203

出　　处：《中西医结合学报》2011年第2期201-208,共8页Journal of Chinese Integrative Medicine

基　　金：supported by Programfor New Century Excellent Talents in University(No.NCET-04-0437);Doctoral Fund of Ministry of Education of China(No.20060268005);Program of Shanghai Subject Chief Scientist(No.08XD14041);Construction Programe of E-Institute of Shanghai Municipal Education Commission(No.E03008);Project of Innovative Research Team of Colleges and Universities of Shanghai(first phase)~~

摘　　要：目的:观察维生素E对氯化汞诱导的大鼠肾间质纤维化的作用并探讨其抗氧化机制方法:32只大鼠随机分为正常组、模型组与维生素E组。除正常组外,其余大鼠以8mg/kg氯化汞(mercuricchloride,HgCl2)灌胃,每天1次,共9周。维生素E组同时以维生素E100mg/kg灌胃,正常组与模型组灌服等量生理盐水。9周后处死大鼠,盐酸水解法检测肾组织羟脯氨酸(hydroxyproline,Hyp)含量,苏木精伊红染色、Masson染色与过碘酸六胺银染色观察肾组织病理形态与胶原沉积;试剂盒方法检测肾组织过氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性与谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)含量;蛋白印迹法检测核因子κB(nuclearfactor-κB,NF-κB)信号途径的κB抑制蛋白(inhibitorκB,IκB)、磷酸化IκB(phospho-IκB,p-IκB)以及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达;蛋白印迹法与免疫荧光法观察α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达。结果:与正常组比较,肾组织Hyp含量、Masson染色与过碘酸六胺银染色以及肾组织α-SMA的变化证实肾间质纤维化模型造模成功;GSH-Px活性与GSH、MDA含量变化提示肾间质纤维化模型存在脂质过氧化损伤。与模型组比较,维生素E组大鼠肾组织Hyp含量降低(P<0.01),肾间质纤维化减轻,GSH与MDA含量降低(P<0.01);维生素E组p-IκB、TNF-α、α-SMA蛋白表达明显降低,各组中IκB蛋白表达无明显变化。结论:维生素E抗氯化汞诱导大鼠肾间质纤维化的作用机制在于抗脂质过氧化损伤,与抑制NF-κB信号通路及细胞外基质产生细胞活化有关。Objective： To observe the effects of vitamin E （Vit E） on mercuric chloride （HgCl2）-induced renal interstitial fibrosis （RIF） in rats and discuss its antioxidative mechanism. Methods： A total of 32 Sprague-Dawley rats were randomly assigned to three groups, normal group, model group and Vit E group. RIF was induced by oral administration of HgCl2 at a dose of 8 mg/kg body weight once a day for 9 weeks. Rats in Vit E group were administered with Vit E capsule at 100 mg/kg body weight, and rats in normal and model groups were treated with normal saline. At the end of the 9th week, rats were sacrificed and renal hydroxyproline （Hyp） content was assayed with Jamall＇s method and collagen deposition was visualized by using hematoxylin and eosin （HE）, Masson＇ s trichrome and periodic acid-silver methenamine （PASM） staining. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, and contents of glutathione （GSH） and malondialdehyde （MDA） in kidney tissue were tested with commercial kits. The expressions of nuclear factor-κB （NF-κB）, inhibitor-κB （κB）, phospho-κB （p-κB） and tumor necrosis factor-α （TNF-α） were determined by Western blot. The expression of e-smooth muscle actin （α-SMA） was assayed by Western blot and immunofluorescent staining. Results. Renal Hyp content, HE, Masson＇ s trichrome and PASM staining results and α-SMA expression confirmed development of HgCl2-induced RIF in rats. Oxidative stress markers GSH, GSH-Px and MDA confirmed oxidative stress in RIF rats. Compared with model rats, rats in Vit E group had lower kidney Hyp content （P〈0. 01）. GSH and MDA contents decreased significantly in Vit E group compared with model group （P〈0. 01）. The expressions of NF-κB and κB had no significant difference among all groups （P〉0. 05）. In Vit E group, the expressions of p-κB and TNF-α decreased significantly compared with model group （P〈0. 01）. The expression of α-SMA in Vit E grou

关 键 词：维生素E 肾间质纤维化 升汞 脂质过氧化反应 动物实验 大鼠 

分 类 号：R965[医药卫生—药理学]