转化生长因子-β1/Smad信号转导途径在大黄酸保护糖尿病大鼠肾脏中的机制探讨

摘要

Objective To study the protective effect of Rhein on the kidney of type 2 diabetic rats induced by high fat diet.Methods A rat model of type 2 diabetes was induced by high fat diet combined with low dose streptozotocin 35 mg/kg.The diabetic rats were randomly divided into diabetes group, Low, middle and high rhein dose groups (50,100,150 mg/kg), metformin group (300 mg/kg) and normal control group.Blood glucose and urine micro albumin were measured at 0, 2, 4 and 8 weeks respectively.Serum creatinine, urea nitrogen, total cholesterol and triglyceride were measured at 8 weeks.HE staining was used to observe the pathological changes of renal tissue.Effects of rhein on the expression of transforming growth factor-β1 and Smad3 protein in renal tissue of diabetic rats were detected with Western Blot.Results The blood glucose and urine micro albumin in model group were significantly higher than those in normal control group.Each rhein dose group exhibited reduced blood glucose and urinary micro albumin in diabetic rats.The high rhein dose group showed significant reduction of blood glucose and urine micro albumin in diabetic rats (P<0.05).Compared with model group, rhein reduced the serum Cr, BUN, TC and TG values in each dose group, most significantly in the high rhein dose group (P<0.05).The obvious pathological changes of renal tissue in model group were observed with most improved changes in the high rhein dose group.The expression of TGF-β1 and Smad3 protein in renal tissue of diabetic rats decreased significantly (P<0.05).Conclusion Rhein has preventive effect on diabetic nephropathy.The mechanism may relate to the improvement of renal function, regulation of blood lipid and down regulation of TGF-β1 and Smad3 protein expression in renal tissue.%目的 研究大黄酸对高脂饮食诱导的2型糖尿病大鼠肾脏的保护作用.方法 采用高脂饮食联合小剂量链脲佐菌素(STZ)35 mg/kg诱导2型糖尿病大鼠模型,分为模型组,大黄酸低、中、高剂量(50、100、150 mg/kg)组,二甲双胍(300 mg/kg)组,另设正常对照组.分别于0、2、4、8周测定大鼠血糖、尿微量白蛋白;8周末检测大鼠血清肌酐(Cr)、尿素氮(BUN)、总胆固醇(TC)与三酰甘油(TG)水平;HE染色观察肾脏组织病理;蛋白印记法检测大黄酸对糖尿病大鼠肾组织转化生长因子-β1(TGF-β1)与Smad3蛋白表达的影响.结果 模型组大鼠血糖及尿微量白蛋白较正常对照组均明显升高,大黄酸各剂量组均能降低糖尿病大鼠血糖及尿微量白蛋白水平,其中,大黄酸高剂量组能显著降低糖尿病大鼠血糖及尿微量白蛋白水平(P<0.05);与模型组相比,大黄酸各剂量组可降低大鼠血清Cr、BUN、TC与TG值,但是大黄酸高剂量组能显著降低糖尿病大鼠血清Cr、BUN、TC与TG值(P<0.05);病理学观察显示模型组大鼠肾组织病变较为明显,大黄酸高剂量组肾组织病变明显改善,且糖尿病大鼠肾组织TGF-β1与Smad3蛋白表达显著下降(P<0.05).结论 大黄酸对糖尿病肾病有预防作用,其机制可能与改善肾功能、调节血脂及下调肾组织TGF-β1与Smad3蛋白的表达有关.