中华医学杂志（英文版）2011，Vol.124Issue(1)：89-94,6.DOI:10.3760/cma.j.issn.0366-6999.2011.01.017
Fluvastatin attenuates myocardial interstitial fibrosis and cardiac dysfunction in diabetic rats by inhibiting over-expression of connective tissue growth factor
Fluvastatin attenuates myocardial interstitial fibrosis and cardiac dysfunction in diabetic rats by inhibiting over-expression of connective tissue growth factor
DAI Qi-ming 1LU Jing 1LIU Nai-feng1
作者信息
- 1. Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China
- 折叠
摘要
Abstract
Background Diabetic myocardiopathy is characterized by myocardial interstitial fibrosis and cardiac dysfunction.Statins were found to exert protective effects on cardiovascular disease by suppressing activation of small G proteins,independently of their lipid-lowering effect. The study investigated the effect of fluvastatin on myocardial interstitial fibrosis, cardiac function and mechanism of its action in diabetic rats.Methods Twenty-four male SD rats were randomly assigned to 3 groups: control rats (n=8), streptozotocin (STZ)-induced diabetic rats (n=8), and diabetic rats treated with fluvastatin (administered fluvastatin orally, 10 mg/kg body weight per day, n=8). Twelve weeks later, miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by picro-sirius red staining, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of connective tissue growth factor (CTGF), and Western blotting was used to detect the protein expression of CTGF. Rho activity was determined by pull-down assay.Results After 12 weeks, the left ventricular systolic pressure (LVSP) and maximum rate of left ventricular (LV) pressure rise and fall (+dP/dt max and -dP/dr max) were significantly lower and left ventricular end diastolic pressure (LVEDP) was higher in the diabetic rats than those in the control rats (P ＜0.01). Moreover, in LV myocardial tissue of diabetic rats the collagen content, fibronectin, mRNA and protein expression of CTGF and the activity of RhoA were all significantly increased compared with the control rats (P ＜0.01). Administration of fluvastain obviously improved the cardiac function of diabetic rats, attenuated fibronectin expression, mRNA and protein expression of CTGF and the activity of RhoA in LV myocardium of diabetic rats.Conclusions Fluvastatin attenuates cardiac dysfunction and myocardial interstitial fibrosis of diabetic rat by inhibiting activity of RhoA to down-regulate the overexpression of CTGF, and Rho/Rho-kinase pathway may be an important target in the treatment of diabetic cardiomyopathy.关键词
HMG-CoA reductase inhibitors/diabetes mellitus/myocardial fibrosis/heart failure/Rho/Rho-kinaseKey words
HMG-CoA reductase inhibitors/diabetes mellitus/myocardial fibrosis/heart failure/Rho/Rho-kinase引用本文复制引用
DAI Qi-ming,LU Jing ,LIU Nai-feng..Fluvastatin attenuates myocardial interstitial fibrosis and cardiac dysfunction in diabetic rats by inhibiting over-expression of connective tissue growth factor[J].中华医学杂志（英文版）,2011,124(1):89-94,6.
