丹芪合剂对糖尿病大鼠肾小管p38MAPK表达的影响

The Effect of Danqi Mixture on Expression of p38 Mitogen-activated Protein Kinase in Renal Tubules of Diabetic Rats

目的:观察丹芪合剂对糖尿病大鼠肾小管p38丝裂原活化蛋白激酶(p38MAPK)和纤维连接蛋白(FN)表达的影响,从而探讨其防治糖尿病肾病的机制。方法:设立正常对照组(NG)、糖尿病组(DG)和糖尿病丹芪合剂治疗组(DQT),链脲佐菌素(STZ)诱导糖尿病模型,12周后测定大鼠血糖、血肌酐和24 h尿蛋白及肾脏指数;PAS染色观察肾脏病理变化;免疫组织化学方法检测肾小管p38MAPK和FN蛋白的表达;RT-PCR方法检测肾皮质p38MAPK mRNA的水平。结果:与NG相比,DG大鼠血糖、血肌酐、24 h尿蛋白及肾脏指数均显著升高,肾小管上皮细胞p38MAPK蛋白及mRNA和FN蛋白表达明显增多,DQT除血糖外,血肌酐和24 h尿蛋白均显著下降,p38MAPK蛋白及mRNA和FN蛋白表达明显减少。结论:丹芪合剂可能通过抑制p38MAPK的表达而减少FN的分泌和沉积,延缓糖尿病肾小管间质损害的进程。

Objective： To observe the effect of Danqi mixture on the expression of p38 mitogen-aetivated protein kinase （p38 MAPK） and fibronectin （FN） in renal tubules of diabetic rats, so as to elucidate the preventing and curative mechanisms of Danqi mixture to diabetic nephropathy. Methods： SD rats were randomly divided into normal group （NG） , diabetes group （DG） and Danqi-treated diabetes group （DQT）. Diabetes model was established by injecting STZ to SD rats. Blood glucose （ BG）, serum creatinine （ Scr）, and 24-hour urine protein （UP） were measured in 12 weeks with biochemical methods, and renal index was calculated. The changes of pathomorphology were examined in PAS-stained kidney sections. Immunohistochemistry was employed to detect the expression of p38 MAPK and FN protein in renal tubules of all groups. The mRNA level of p38MAPK in renal cortex was examined by RT-PCR. Results： Compared those in group NG, the levels of BG, Scr, 24-hour UP and kidney index were remarkably higher in group DG, and the expression of p38 MAPK （protein and mRNA） and FN （protein） were also increased apparently in renal tubular cells in group DG, which were decreased notably in group DQT compared with those in group DG, except BG. Conclusion： Danqi mixture can inhibit the expression of p38 MAPK in renal tubule cells, and therefore reduce the deposition of FN and delay the process of tubulointerstitial injury in the kidney of diabetic rats.