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目的研究通心络对糖尿病肾病大鼠肾脏组织结缔组织生长因子(CTGF)及骨形态蛋白7(BMP-7)表达的影响,并探讨其对糖尿病大鼠肾脏保护作用及机制。方法采用链脲佐菌素(STZ)诱导建立糖尿病大鼠模型,造模成功后随机分为糖尿病组(DM组),通心络治疗组(TXL组),正常大鼠为对照组(C组),于24周末检测各组大鼠、24h尿微量蛋白、空腹血糖(FPG)、血清糖基化血红蛋白I(HbA1c)、晚期糖基化终末产物(AGEs)、尿素氮(BUN)、肌酐(Cr)、肾质量/体质量(KW/BW),光镜PAS染色,采用RT-PCR及Westernblot测定CTGF、BMP-7mRNA及蛋白的表达水平。结果与C组比较,DM组大鼠24周后KW/BW、尿微量蛋白、血清AGEs、BUN、Cr、HbA1c均显著性升高(P<0.05);TXL组较DM组KW/BW、尿微量蛋白显著降低(P<0.05);肾脏组织学观察显示,DM组肾小球基底膜增厚,系膜区细胞外基质(ECM)沉积增多,肾小管上皮细胞水肿现象明显,经通心络治疗后,肾脏病理改变显著减轻。另外,DM组大鼠肾组织BMP-7基因和蛋白表达下降,而CTGF基因和蛋白表达升高;与DM组比较TXL组能够抑制CTGF表达,使BMP-7表达升高。结论通心络可以减轻糖尿病大鼠尿微量蛋白、改善肾脏组织病理,对DN大鼠肾脏具有保护作用,其机制可能与抑制CTGF,上调BMP-7表达有关。
Objective To study the effect of Tongxinluo on the expression of connective tissue growth factor (CTGF) and bone morphogenetic protein 7 (BMP-7) in kidney of diabetic nephropathy rats and to explore its protective effect on diabetic nephropathy and its mechanism. Methods Diabetic rats were induced by streptozotocin (STZ). The rats were randomly divided into diabetic group (DM group), Tongxinluo treatment group (TXL group) and normal control group (C group) ), 24 h urine microalbumin, fasting blood glucose (FPG), serum glycosylated hemoglobin I (HbA1c), advanced glycation end products (AGEs), blood urea nitrogen (BUN), creatinine (Cr), kidney mass / body weight (KW / BW) and PAS staining. The expression of CTGF, BMP-7 mRNA and protein were detected by RT-PCR and Western blot. Results Compared with group C, KW / BW, urinary microalbumin, serum AGEs, BUN, Cr and HbA1c in DM group were significantly increased after 24 weeks (P <0.05) (P <0.05). Histological examination showed that glomerular basement membrane thickening, mesangial extracellular matrix (ECM) deposition and tubular epithelial cell edema were obvious in DM group. After treatment, the renal pathological changes significantly reduced. In addition, the expression of BMP-7 gene and protein in the DM group decreased and the expression of CTGF gene and protein increased in the DM group. Compared with the DM group, the TXL group inhibited the expression of BMP-7 and increased the expression of BMP-7. Conclusion Tongxinluo can reduce urinary microalbuminuria in diabetic rats and improve renal histopathology, which may have a protective effect on the kidneys of DN rats. The mechanism may be related to the inhibition of CTGF and the up-regulation of BMP-7 expression.