Regulatory effect of compound Coptidis Rhizoma capsule on unbalanced expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway in rats with early diabetic nephropathy

Abstract

To investigate the effect of compound Coptidis Rhizoma capsule (CCRC) on unbalanced expression of renal tissue TGF-β1/BMP-7 and Smad signaling pathway in rats with early diabetic nephropathy (DN), and discuss CCRC's effect on DN rats with early diabetic nephropathy and its possible mechanism. DN model rats were established by injecting streptozotocin (STZ). The rats were randomly divided into seven groups: the normal group, the model group, the enalapril treatment group, the xiaoke pill treatment group and three CRCC treatment groups. They were orally administered once a day for five weeks. The fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), insulin (Ins), 24 h urinary protein (24 h Upro) and 24 h urinary microalbumin (24 h UmAlb) were tested. The pathological changes in renal tissues were examined by optical microscopy. Immuno- histochemical measures were used to detect the expressions of TGF-β1, BMP-7, Smad2/3, Smad1/5, and Smad7 protein, and RT-PCR was used to detect TGF-β1 mRNA and BMP-7 mRNA in renal tissues. Compared with model group, BUN, Scr, Ins, 24 h Upro and 24 h UmAlb levels decreased at different degrees in CCRC treatment groups; the abnormal pathomorphology in renal tissue was improved; immunohistochemistry results showed that the expression of TGF-β1 and Smad2/3 were reduced, while the expression of BMP-7, Smad1/5 and Smad7 increased in CRCC treatment groups; the expression of TGF-β1 mRNA were reduced, but the expression of BMP-7 mRNA had no obvious change in CRCC treatment groups. CRCC can improve the early renal function, delay the progression of chronic renal pathology and maintain the dynamic balance of TGF-β1/BMP-7 expression in renal tissues of DN rats. The mechanism may be related to down-regulation of renal TGF-β1 and up-regulation of BMP-7 through Smad signaling pathway.