吉林大学学报(医学版) ›› 2017, Vol. 43 ›› Issue (03): 512-517.doi: 10.13481/j.1671-587x.20170310

• 基础研究 • 上一篇    下一篇

五味子提取物对糖尿病大鼠肾脏组织中基质金属蛋白酶表达的影响及其肾脏保护作用

杨江辉1,2, 孙成博1, 耿嘉男1, 李秋杰1, 朱尧1, 陈兴兴1, 陈安天1, 于晓艳1   

  1. 1. 吉林大学药学院实验药理与毒理学教研室, 吉林 长春 130021;
    2. 北京清华长庚医院病理科 清华大学医学中心, 北京 102218
  • 收稿日期:2016-09-09 出版日期:2017-05-28 发布日期:2017-06-01
  • 通讯作者: 于晓艳,副教授,硕士研究生导师(Tel:0431-85619702,E-mail:yuxy@jlu.edu.cn) E-mail:yuxy@jlu.edu.cn
  • 作者简介:杨江辉(1982-),男,河南省新乡市人,主管技师,医学硕士,主要从事基础病理学方面的研究。
  • 基金资助:
    吉林省科技厅科技发展计划项目资助课题(20160101206JC);吉林大学大学生创新创业训练计划资助课题(2016B73764)

Effect of extract of Schisandra chinensis on expression of matrix metalloproteinase in kidney tissue of diabetic rats and its protective effect on kidney tissue

YANG Jianghui1,2, SUN Chengbo1, GENG Jianan1, LI Jiujie1, ZHU Yao1, CHEN Xingxing1, CHEN Antian1, YU Xiaoyan1   

  1. 1. Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun 130021, China;
    2. Department of Pathology, Beijing Tsinghua Changgeng Hospital, Medical Center, Tsinghua University, Beijing 102218, China
  • Received:2016-09-09 Online:2017-05-28 Published:2017-06-01

摘要: 目的:探讨五味子提取物对糖尿病大鼠肾脏组织中基质金属蛋白酶(MMPs)表达的影响,从基质降解角度阐明其肾脏保护作用。方法:采用链脲佐菌素(STZ)复制糖尿病大鼠模型,45只糖尿病模型大鼠随机分为模型组、五味子组和贝那普利组,每组15只;另取15只大鼠作为正常对照组。给药12周后检测各组大鼠常规血、尿生化指标及组织学改变;检测各组大鼠血清和肾组织匀浆中血糖(BG)、血尿素氮(BUN)、血肌酐(Scr)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(T-CHO)、甘油三酯(TG)水平和尿白蛋白、尿总蛋白排泄率;免疫组织化学法检测大鼠肾组织中纤维连接蛋白(FN)、Ⅳ型胶原蛋白(Col Ⅳ)、基质金属蛋白酶抑制剂2(TIMP-2)的表达量;酶谱法检测大鼠肾组织中MMP-2活性。结果:与模型组比较,五味子组大鼠肾小球系膜聚集等现象明显减轻,尿白蛋白排泄率、LDL-C及血清丙二醛(MDA)水平均明显降低(P<0.05),肾组织中过氧化氢酶(CAT)(P<0.01)和超氧化物歧化酶(SOD)活性升高(P<0.05),MDA水平降低(P<0.05)。免疫组织化学检测,与模型组比较,五味子组大鼠肾组织中FN、Col Ⅳ和TIMP-2表达量明显降低。酶谱法检测,与模型组比较,五味子组和贝那普利组大鼠肾组织中MMP-2活性明显升高(P<0.05)。结论:五味子提取物对STZ导致的实验性糖尿病大鼠的肾脏有保护作用,其机制可能与抑制氧化应激、提高MMP-2活性、抑制TIMP-2表达从而改善基质降解有关。

关键词: 五味子提取物, 糖尿病肾病, 基质金属蛋白酶, 基质金属蛋白酶抑制剂

Abstract: Objective: To investigate the effect of the extract of Schisandra chinensis on the matrix metalloproteinases(MMPs) system in kidney tissue of the diabetic rats,and to explore its protective effect on the kidney tissue from the matrix degradation perspective. Methods: STZ was used to establish rat models of diabetes mellitus. A total of 45 diabetic rats were randomly divided into model group,extract of Schisandra chinensis group and Benazepril group,and there were 15 rats in each group.Another 15 rats were selected and used as normal control group.12 weeks after administration,the routine blood and urine biochemical indexes,the histological changes,blood glucose (BG), blood urea nitrogen(BUN),serum creatinine(Scr),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterin(LDL-C),total cholesterol(T-CHO),and triglyceride(TG) levels, excretion rates of albuminuria and proteinuria of the rats in various groups were detected; the expression amounts of fibronectin (FN),type Ⅳ collagen (Col Ⅳ),and matrix metalloproteinase inhibitor metalloproteinase-2 (TIMP-2) in kidney tissue of the rats were detected by immunohistochemical method; the activity of matrix metalloproteinase-2 (MMP-2) was detected by zymography. Results: Compared with model group,the glomeruli matrix accumulation of the rats in extract of Schisandra chinensis group was significantly improved,the excretion rate of albuminuria,LDL-C level and serum MDA level were decreased(P<0.05),the activities of CAT(P<0.01)and SOD(P<0.05)in kidney tissue were increased,and the level of MDA in kidney tissue was decreased(P<0.05). The immunohistochemistry results showed that compared with model group,the expression amounts of FN,Col Ⅳ,and TIMP-2 in kidney tissue of the rats in extract of Schisandra chinensis group were significantly decreased.The zymography results showed that compared with model group,the activity of MMP-2 in kidney tissue of the rats in extract of Schisandra chinensis group was significantly increased(P<0.05). Conclusion: Extract of Schisandra chinensis has protective effect on the kidney tissue of the diabetic rats induced by STZ,and the mechanism may be related to the inhibition of oxidative stress and the improvement of MMP-2 activity as well as the inhibition of TIMP-2 expression which could improve the matrix degradation.

Key words: extract of Schisandra chinensis, matrix metalloproteinase, matrix metalloproteinase inhibitor, diabetic nephropathy

中图分类号: 

  • R587.2