Zhang Li-na, Xie Xi-sheng, Zuo Chuan, Fan Jun-ming
Department of Nephrology, State Key Laboratory of Biotherapy of Human Disease, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 May;40(3):466-71.
To investigate the effects of Ginsenoside Rgl on proteinuria and the expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in rats with diabetic nephropathy (DN).
The DN rat model was established by injection of streptozotocin (STZ, 65 mg/kg) in abdominal cavity. Forty Sprague-Dawley male rats were randomly divided into 4 groups: normal group, DN group, Ginsenoside Rgl 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. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to examine the protein expression levels of MCP-1 and TNF-alpha, respectively. The mRNA of TNF-alpha and MCP-1 were reverse transcribed and quantified by real-time PCR.
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-alpha 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-alpha in the rats in the DN group and the two treatment groups were significantly higher than those in the normal group (P<0.05). The rats in the treatment groups had lower levels of expression of MCP-1 and TNF-alpha than those in the DN group (P<0.05). The correlation analysis indicated that the levels of MCP-1 and TNF-alpha were positively related to twenty-four hours urine protein (r=0.7802, 0.6963), glomerular sclerosis index (r=0.8296, 0.7413) and thickness of podocyte membrane (r=0.7678, 0.6701, P<0.05).
Ginsenoside Rgl reduces the expression of MCP-1 and TNF-alpha, repairs the pathological lesions of podocyte and nephron, and reduces the twenty-four hour urine protein rats with diabetic nephropathy.
探讨人参皂苷Rg1对糖尿病肾病（DN）大鼠蛋白尿及单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）表达的影响。
通过腹腔注射链脲佐菌素（STZ，65mg/kg）建立DN大鼠模型。40只雄性Sprague-Dawley大鼠随机分为4组：正常组、DN组、人参皂苷Rg1治疗组和厄贝沙坦治疗组。常规监测血糖。治疗8周后处死大鼠，处死前一天测定24小时尿蛋白和血清肌酐。评估肾脏病理及足细胞变化。分别采用免疫组化和酶联免疫吸附测定（ELISA）检测MCP-1和TNF-α的蛋白表达水平。采用实时荧光定量PCR对TNF-α和MCP-1的mRNA进行逆转录和定量分析。
DN大鼠肾小球体积增大、基底膜增厚、系膜基质增多，肾小球内可见一些炎性细胞。与正常组相比，DN组足细胞数量显著减少（P<0.01）。与DN组相比，两个治疗组基底膜变薄，足细胞数量增加（P<0.05）。DN组及两个治疗组大鼠的24小时尿蛋白、血清肌酐、血糖、血清MCP-1和TNF-α水平均显著高于正常大鼠（P<0.05）。治疗组大鼠的24小时尿蛋白和血清肌酐水平低于DN组大鼠（P<0.05）。但血糖变化不大（P>0.05）。两个治疗组之间无差异。免疫组化、ELISA和实时荧光定量PCR结果显示，DN组及两个治疗组大鼠MCP-1和TNF-α的表达水平均显著高于正常组（P<0.05）。治疗组大鼠MCP-1和TNF-α的表达水平低于DN组（P<0.05）。相关性分析表明，MCP-1和TNF-α水平与24小时尿蛋白（r=0.7802，0.6963）、肾小球硬化指数（r=0.8296，0.7413）和足细胞膜厚度（r=0.7678，0.6701，P<0.05）呈正相关。
人参皂苷Rg1降低MCP-1和TNF-α的表达，修复足细胞和肾单位的病理损伤，降低糖尿病肾病大鼠的24小时尿蛋白。
