还原型谷胱甘肽对马兜铃酸肾病小鼠肾脏的影响  

The impact of glutathione on aristolochic acid nephropathy mice

作　　者：王瑾珺[1] 徐自强[1] 倪晓洁[1] 蔡勇[1] 夏鹏[1] 郑少玲[1] 

机构地区：[1]温州医科大学附属第一医院移植科,325000

出　　处：《实用医学杂志》2016年第21期3524-3527,共4页The Journal of Practical Medicine

基　　金：温州市科技局基金资助项目(编号:Y20130199)

摘　　要：目的:研究还原型谷胱甘肽(GSH)对马兜铃酸肾病(AAN)小鼠肾脏的保护作用及其机制。方法:将36只C56BL/6小鼠随机分为空白对照组、对照组(AA组)及GSH组,每组12只。空白对照组隔天腹腔注射生理盐水5 mL持续6周,之后改为5 mL/d持续4周。AA组及GSH组小鼠按5 mg/kg剂量,隔天腹腔注射0.5 mg/mL含有AA-I的工作液,持续6周建模。建模后AA组腹腔注射生理盐水5 mL/d持续4周,GSH组腹腔注射GSH持续干预4周,剂量为800 mg/(kg·d)。于第6、10周检测小鼠血清肌酐及尿素氮,后处死小鼠,取肾组织切片行HE染色,用免疫组织化学方法检测肾组织中α-平滑肌肌动蛋白(α-SMA)和含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)蛋白的表达。结果 :同AA组相比,GSH组小管上皮细胞变性坏死较AA组明显减轻;GSH组血肌酐及尿素氮较AA组均显著降低(P<0.05);AA组和GSH组的α-SMA及Caspase-3蛋白表达水平均显著高于空白对照组(P<0.05),而GSH组较AA组显著降低(P<0.05)。结论 :GSH可以显著减轻AA导致的肾毒性,减少肾小管上皮细胞凋亡,抑制肾小管间质纤维化和肾小管上皮细胞转分化,改善并延缓AAN的进展,对AAN肾脏起到保护作用。Objective To study the protective effects of glutathione （GSH） on aristolochic acid nephropathy （AAN） in mice and its functioning mechanisms. Methods 36 C56BL/6 mice were randomly divided into blank control group, AA group and GSH treatment group, with 12 mice in each group. The blank control group received intraperitoneal injection of normal saline for 6 weeks, followed by 5 mL/d for 4 weeks. AA group and GSH treatment group mice received intraperitoneal injection of 0.5 mg/mL working fluid containing AA-I with 5 mg/kg dose every other day for 6 weeks to create AAN mice model. After the model was established, AA group received intraperitoneal injection of normal saline for 4 weeks, and the GSH treatment group received intraperitoneal injection of GSH for 4 weeks, and the dose was 800 mg/（kg.d）. On the 6th week and 10th week, the serum creatinine （SCr） and blood urea nitrogen （BUN） were detected. All mice were sacrificed and the renal tissue sections were stained with hematoxylin and eosin （HE） staining, with renal tissues were determined by immunohistochemical method for expressions of α-smooth muscle aetin （α-SMA） and containing eysteine aspartic acid protein hydrolytic enzyme-3 （Caspase-3）. Results Compared with AA group, the degeneration and necrosis of tubular epithelial cells significantly reduced in GSH group; the SCr and BUN levels significantly decreased in GSH group than in AA group （P 〈 0.05）; expressions of α-SMA and Caspase-3 in AA group and GSH group were significantly higher than those in the blank control group （P 〈 0.05）, while those decreased significantly in GSH group compared to those of AA group（P 〈 0.05）. Conclusions GSH can significantly reduce AA＇s renal toxicity and the apoptosis of renal tubular epithelial cells, inhibit the renal tubule interstitial fibrosis and renal tubular epithelial cells＇ transition, improve and delay the progression of AAN, take protective effects to the AAN kidney.

关 键 词：马兜铃酸肾病 谷胱甘肽硫-转移酶 还原型谷胱甘肽 

分 类 号：R692[医药卫生—泌尿科学]