丹芪合剂对DM大鼠肾小管BMP-7及其受体表达影响.docVIP

丹芪合剂对DM大鼠肾小管BMP-7及其受体表达影响 　 作者：肖瑛，石明隽，桂华珍，郭兵，张国忠 【摘要】 　　目的观察丹芪合剂和依那普利对糖尿病（DM）大鼠肾小管上皮细胞骨形态发生蛋白-7（BMP-7）及其受体ALK-3表达的影响，探讨丹芪合剂的药理机制。方法将SD大鼠分为正常对照组（A组）、糖尿病组（B组）、糖尿病丹芪合剂组（C组）和糖尿病依那普利组（D组）。以链脲佐菌素复制DM大鼠模型。于实验12周处死大鼠后测定相应生化指标和肾脏指数，PAS染色观察肾组织的形态结构变化；免疫组化检测肾小管上皮细胞BMP-7和FN蛋白的表达；RT-PCR方法检测肾皮质BMP-7和ALK-3 mRNA水平。结果①B组的血糖、甘油三酯和总胆固醇、血肌酐、肾脏指数均显著高于A组并出现明显的蛋白尿，C和D组上述指标除血糖外均明显低于B组。②免疫组化结果显示BMP-7蛋白高表达于A组肾小管上皮细胞胞浆，FN仅有少量表达；B组BMP-7蛋白的表达明显减少，FN表达却明显增多；C和D组肾小管上皮细胞BMP-7蛋白表达显著高于B组，但低于A组，同时FN的表达减少。③RT-PCR结果显示，与A组相比，B组肾皮质BMP-7表达明显减少，且ALK-3 mRNA未见表达，C和D组BMP-7及其受体ALK-3 mRNA表达均显著高于B组，D组ALK-3 mRNA表达甚至高于A组。结论丹芪合剂和依那普利可能通过促进内源性BMP-7及其受体ALK-3的表达,使FN的沉积减少,从而对糖尿病大鼠肾脏起保护作用。 【关键词】 糖尿病肾病； 骨形态发生蛋白-7； ALK-3； 丹芪合剂； 依那普利 　　Abstract：ObjectiveTo investigate the effects of Dan qi mixture and enalapril on the expression of bone morphogenetic protein-7(BMP-7) and its receptor ALK-3 in the renal tubules of diabetic rats. Methods SD rats were randomly divided into normal control group (group A), diabetic group (group B), diabetic Danqi-treated group (group C), diabetic enalapril-treated group (group D). The diabetic rat model was made with streptozotocin .After 12 weeks, blood glucose, triglyceride, cholesterol and creatinine, urine protein were analyzed with biochemical methods. Kidney index was analyzed as well. The changes of pathomorphology were examined in PAS staining sections. Immunohistochemistry was employed to detect the expression of BMP-7 and FN protein in renal tubules of all groups. The mRNA levels of BMP-7 and its receptor ALK-3 in renal cortex were examined by RT-PCR. Results①Compared with group A, the levels of blood glucose, triglyceride, cholesterol and creatinine, urine protein and kidney index were increased remarkably in group B. In group C and D, parameters above-mentioned except blood glucose were notably cut down. ② The expression of BMP-7 protein was high and FN protein was slight by immunohistochemistry in group A. On the other hand, the protein of BMP-7 was decreased remarkably in group B