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

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。

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

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.