缬沙坦联合辛伐他汀对早期糖尿病肾病大鼠肾脏的保护作用

Protection of vaisartan combined with simvastatin on the kidney in early diabetic nephropathy rats

目的探讨降脂药辛伐他汀及血管紧张素Ⅱ受体拮抗剂类药物缬沙坦对早期糖尿病肾病大鼠肾脏的保护作用。方法用链脲佐菌素（STZ）诱导糖尿病肾病大鼠模型，将SD大鼠随机分成5组，每组10只：正常对照组（C组）、糖尿病肾病组（D组）、缬沙坦组（x组）、辛伐他汀组（Z组）和缬沙坦及辛伐他汀联合组（L组）。5周末检测5组大鼠血糖（BG）、糖化血红蛋白（HbA1C）、总胆固醇（TC）、甘油三酯（TG）、血尿素氮（BUN）、肌酐（SCr）、肌酐清除率（Ccr）、尿白蛋白排泄率（UAER）等指标的变化；利用透射电子显微镜观察肾脏足细胞超微病理结构。结果D组与c组比较，BG[分别为（20．3±3．2）、（6．1-t-O．4）mmol／L]、HbA1c[分别为（7．184-0．47）％、（3．37±0．15）％]、TC[分别为（2．69±0．35）、（1．28±0．24）mmol／L]、TG[分别为（3．09±0．37）、（1．18±0．25）mmol／L]明显升高（P均〈0．05）；D组Ccr[（0．89±0．19）ml／min]较C组[（1．27±0．33）ml／min]和X、Z、L组显著下降（P〈0．05），D组大鼠UAER[（19．87±3．85）μg／24h]明显高于C组[（3．67±1．01）μg／24h]（P〈0．05），X、Z、L组大鼠UAER显著低于D组（P〈0．05），而L组改善尤其显著（P〈0．05）；D组的足细胞足突严重融合，X、Z、L组仅少量足突融合较D组改善，而L组改善尤其显著。结论缬沙坦及辛伐他汀单用及联合应用，尤其是联合用药对早期糖尿病大鼠肾脏有保护作用。

Objective To explore the protection of valsartan combined with simvastatin on kidney in early diabetic nephropathy rats. Methods Diabetic nephropathy rats model were induced by streptozocin （STZ） ,the experimental rats were randomly divided into 5 groups： control （group C）, diabetic nephropathy （ group D）, diabetes treated with valsartan （ group X）, diabetes treated with simvastatin （ group Z）, and diabetes treated with combined valsartan and simvastatin （ group L ）. Blood glucose （ BG ）, HbAl e, blood cholesterol （ TC）, trigalloylglycerol （ TG）, blood ureanitrogen （ BUN ）, serum creatinine （ SCr ） , urinary albumin excretion rate （UAER） were measured, and the podocyte ultrastructure was observed by transmission electronic microscopy. Results The levels of BG, HbA1c, TC, TG and UAER in group D increased significantly compared to group C（BG：[20.3 ±3.2]mmol/L vs [6.1±0.4]mmol/L;HbA1c：[7.18±0.471% vs [3.37±0. 151% ;TC： [2. 69 ±0. 35 ] mmol/L vs [ 1.28 ±0. 24] mmol/L;TG： [3.09 ±0. 37 ] mmol/L vs [ 1.18 ±0. 25] mmol/L） （P 〈 0. 05 ）. Creatinine clearance rates （Ccr） in group D （ [ 0. 89 ± 0. 19 ] ml/min ） decreased significantly compared to group C（ [ 1.27 ±0. 33 ] ml/min） ,as well as group X,Z and L（ Ps 〈 0. 05 ）. UAER in group D was significantly higher than that in group C （ [ 19. 87± 3.85 ] μg/24 h vs [ 3. 67 ± 1.01 ]μg/24 h） （P 〈0. 05 ）, as well as group X, Z and L （ P 〈 0. 05 ）, and the improvement in group L was particularly significant （ P 〈 0. 05 ） . The projections of podoeyte in group D severely syncretized, there were slightly improvement in group X, Z and L compared to group D, and the improvement in group L was remarkable. Conclusion The treatment with valsartan, simvastatin and their combination will effectively protect the kidney in early diabetic nephropathy rats, and the effect of using the combination therapy is much better.