人参皂甙Rg1对糖尿病肾病大鼠TNF-α、MCP-1表达的影响  

Effect of Ginsenoside Rgl on the Expression of TNF-α and MCP-1 in Rats with Diabetic Nephropathy

作　　者：张丽娜[1] 谢席胜[1] 左川[1] 樊均明[1,2] 

机构地区：[1]四川大学华西医院肾脏内科,成都610041 [2]四川大学华西医院人类疾病生物治疗国家重点实验室

出　　处：《四川大学学报（医学版）》2009年第3期466-471,共6页Journal of Sichuan University(Medical Sciences)

基　　金：教育部博士点基金(项目编号200610063)资助

摘　　要：目的观察人参皂甙Rg1对糖尿病肾病大鼠尿蛋白以及炎症因子肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子蛋白-1(MCP-1)表达的影响。方法将40只雄性SD大鼠随机分为4组:正常对照组、糖尿病模型组、人参皂甙Rg1治疗组、厄贝沙坦(ARB)治疗组。采用链脲佐菌素(65mg/kg)腹腔注射建立糖尿病大鼠模型。于动物处死前1d测血糖,用代谢笼收集24h尿液,记录尿量行24h尿蛋白定量和肾功检查。光镜及电镜观察肾组织的病理变化。采用酶联免疫吸附法(ELISA)检测血MCP-1、血及肾TNF-α水平;免疫组织化学检测肾脏组织MCP-1蛋白的表达;实时荧光定量PCR(real-ti me PCR)检测肾脏组织中MCP-1、TNF-α基因水平的表达。结果模型组大鼠镜下见肾小球体积增大,基底膜增厚及系膜物质增多,足细胞较正常对照组减少(P<0.01)。两治疗组与模型组分别比较,肾小球基底膜未见明显增宽,足细胞数增加(P<0.05)。两治疗组之间无明显差异。模型组大鼠血糖、24h尿蛋白、血肌酐水平升高,与对照组相比差异有统计学意义(P<0.05)。两治疗组与模型组相比,血糖水平无明显变化(P>0.05),但24h尿蛋白、血肌酐水平均有所改善(P<0.05)。免疫组织化学、ELISA和real-ti me PCR结果表明,与对照组相比,模型组MCP-1、TNF-α的表达增加(P<0.05),两治疗组MCP-1、TNF-α表达较模型组减少(P<0.05),但两治疗组无明显差异。相关性分析提示MCP-1、TNF-α水平与24h尿蛋白水平(r=0.7802,0.6963)、肾小球硬化指数(r=0.8296,0.7413)、足细胞基底膜厚度(r=0.7678,0.6701)成正相关(P<0.05)。结论人参皂甙Rg1能降低TNF-α、MCP-1的水平,改善糖尿病肾病大鼠足细胞及肾脏的病理损害,能显著减少糖尿病大鼠24h尿蛋白,具有一定的肾保护作用。Objective To investigate the effects of Ginsenoside Rg1 on proteinuria and the expression of monocyte chemotactie protein-1 （MCP-1）and tumor necrosis factor-α （TNF-α）in rats with diabetic nephropathy （DN）. Methods The DN rat model was established by injection of streptozotoein（STZ, 65 mg/kg）in abdominal cavity. Forty Sprague-Dawley male rats were randomly divided into 4 groups： normal group, DN group, Ginsenoside Rg1 treatment group and Irbesartan treatment group. The blood glucose was monitored routinely. Twenty-four hours urine protein and serum creatine were measured the day before the rats were killed when the eight weeks of treatments had been completed. The renal pathological and podocyte changes were evaluated. Immunohistochemisty and euzymelinked immunosorbent assay （ELISA） were performed to examine the protein expression levels of MCP- 1 and TNF-α, respectively. The mRNA of TNF-α and MCP-1 were reverse transcribed and quantified by real-time PCR. Results The DN rats had increased volume of renal glomerulus, thickened basement membrane, and increased mesenterium mass, as well as some inflammatory cells in renal glomerulus. The number of potocyte decreased significantly in the DN group compared with the normal group （P〈0.01）. Compared with the DN group, the basement membrane became thinning and the number of podocyte increased in the two treatment groups （P〈 0.05）. The rats in the DN group and the two treatment groups had significantly higher levels of twenty-four hour urine protein, serum creatine, serum glucose, serum MCP-1 and TNF-α than the normal rats （P〈0.05）. The rats in the treatment groups had lower levels of twenty-four hours urine protein and serum creatine than the rats in the DN group （P〈0.05）. But the serum glucose had little changes （P〉0.05）. There was no difference between the two treatment groups. Immunohistochemisty, ELISA and real-time PCR results indicated that the expression levels of MCP-1 and TNF-α in the rats in the DN group

关 键 词：人参皂甙RG1 糖尿病肾病 肿瘤坏死因子-Α 单核细胞趋化因子蛋白-1 蛋白尿 

分 类 号：R285.5[医药卫生—中药学]