OBJECTIVE

2

To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in rats with diabetic nephropathy （DN）.

METHODS

2

Eight rats were selected as control group （ordinary feed）， the remaining rats were given high-glucose and high-fat diet combined with ip injection of streptozotocin （35 mg/kg） to induce DN model. Model rats were randomly divided into model group （purified water）， irbesartan group （positive control， 14.12 mg/kg） and Tongxinluo capsule group （0.3 g/kg）， including 12 rats in the model group and 11 rats for each of the other two groups. All groups were given relevant medicine or water intragastrically， once a day， for 16 consecutive weeks. After the last medication， fasting blood glucose and 24 h urinary total protein （24 h UTP） were detected. Pathological changes in renal cortex of rats in each group were observed. Serum levels of tissue-type plasminogen activator （PA） and plasminogen activator inhibitor 1 （PAI-1） were measured. mRNA expressions of transforming growth factor-β

1

（TGF-β

1

）， type Ⅳ collagen（COL-Ⅳ）， Wnt4 and

β

-catenin in renal cortex of rats were detected. The protein depositions or expressions of TGF-β

1

， COL-Ⅳ， focal adhesion kinase （FAK）， integrin-linked kinase （ILK）， E-cadherin， PA， PAI-1， Wnt4 and

β

-catenin in renal cortex of rats were observed or determined.

RESULTS

2

Compared with model group， 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced （

P

＜0.05）； pathological damage and fibrosis of renal cortex were relieved； the expression of PA in serum and renal cortex was significantly increased， while PAI-1 level was significantly reduced （

P

＜0.05）； the depositions of COL-Ⅳ and TGF-β

1

in r

enal cortex were all reduced， and corresponding mRNA expression was decreased significantly （

P

＜0.05）； the depositions of ILK and FAK were decreased， while the deposition of E-cadherin was increased； protein and mRNA expressions of Wnt4 and

β

-catenin were significantly reduced （

P

＜0.05）.

CONCLUSIONS

2

Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model rats， and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity， the decrease of ILK and FAK expression， and inhibition of Wnt/

β

-catenin signaling pathway.