[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]

Zhongguo Zhong Yao Za Zhi. 2015 Mar;40(5):938-45.
[Article in Chinese]

Abstract

Objective: 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.

Method: 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.

Result: 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.

Conclusion: 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.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 7 / genetics
  • Bone Morphogenetic Protein 7 / metabolism*
  • Coptis / chemistry*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rhizome / chemistry
  • Signal Transduction / drug effects*
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Bone Morphogenetic Protein 7
  • Smad Proteins
  • Transforming Growth Factor beta1