缬沙坦对糖尿病大鼠肾脏的保护作用与机制探讨

Study on protective effects and mechanisms of valsartan on rat diabetic nephropathy

目的探讨缬沙坦对糖尿病大鼠肾脏病变的影响及其作用机制。方法将20只糖尿病大鼠随机分为糖尿病组(DM组)、糖尿病缬沙坦治疗组(DMV组),无糖尿病大鼠作为正常对照组(NC组)。12周后,取血测定血糖(BG)、三酰甘油(TG)、总胆固醇(TC)、血肌酐(Scr)、尿素氮(BUN)及24h尿清蛋白(UAE)。光镜下观察肾小球形态、结构并计算平均肾小球截面(MGA)、平均肾小球体积(MGV)。免疫组织化学法检测肾组织单核细胞趋化蛋白-1(MCP-1)表达。结果大鼠BG、TG、TC、Scr、BUN、UAE及肾组织MCP-1表达DM组分别为(18.30±0.82)mmol/L、(1.97±0.08)mmol/L、(3.22±0.07)mmol/L、(41.0±2.16)μmol/L、(9.87±0.19)mmol/L、(25.99±0.52)mg/24h、12.17±1.94,DMV组分别为(17.89±0.79)mmol/L、(1.94±0.06)mmol/L、(3.20±0.05)mmol/L、(38.9±0.99)μmol/L、(9.05±1.02)mmol/L、(19.87±0.78)mg/24h、9.08±1.2,与对照组[(6.10±0.06)mmol/L、(0.58±0.04)mmol/L、(1.41±0.07)mmol/L、(32.9±2.13)μmol/L、(6.60±0.37)mmol/L、(4.95±0.27)mg/24h、1.19±0.70]比较差异有统计学意义(P<0.05);肾组织MCP-1蛋白表达与24h尿UAE定量呈正相关(r=0.943,P<0.05);与Scr水平呈正相关(r=0.823,P<0.05)。结论缬沙坦对糖尿病大鼠肾脏病变有一定的保护作用。抑制MCP-1蛋白表达,可能是其保护作用机制之一。

Objective To study the effects of valsartan on diabetic nephropathy in rats and to explore its action mechanisms.Methods High-fat diet in combination with abdominal injection of low-dose of streptozocin（STZ）was used to induce diabetes in Wistar rats.Diabetic rats were randomly divided into none-treated group（DM）and valsartan treated group（DMV）.None diabetic normal Wistar rats were served as controls（NC）.After 12 weeks of treatment,blood glucose（BG）,triglyceride（TG）,total cholesterol（TC）,serum creatinine（Scr）,urea nitrogen（BUN）and 24 h urinary albumin excretion（UAE）were measured.HE staining was performed on renal tissues for light microscopy examination of glomerular structure and measurements of mean glomerular area（MGA）and mean glomerular volume（MGV）.The expression of MCP-1 was detected by immunohistochemical method.Results Serum BG,TG,TC,Scr,BUN,UAE and MCP-1 expression in renal tissues were（18.30±0.82）mmol/L,（1.97±0.08）mmol/L,（3.22±0.07）mmol/L,（41.0±2.16）μmol/L,（9.87±0.19）mmol/L,（25.99±0.52）mg/24 h and 12.17±1.94 in the DM group;（17.89±0.79）mmol/L,（1.94±0.06）mmol/L,（3.20±0.05）mmol/L,（38.9±0.99）μmol/L,（9.05±1.02）mmol/L,（19.87±0.78）mg/24 h and 9.08±1.2 in the DMV group;（6.10±0.06）mmol/L,（0.58±0.04）mmol/L,（1.41±0.07）mmol/L,（32.9±2.13）μmol/L,（6.60±0.37）mmol/L,（4.95±0.27）mg/24 h and 1.19±0.70 in the control group,showing statistical difference（P0.05）.The MCp-1 expression in renal tissues was positively correlated with UAE and Scr（r=0.943;r=0.823,P0.05）.Conclusion Valsartan has the protective effects on diabetic nephropathy.One of the mechanisms may be thought to be the suppression of the renal MCP-1 expression.