Experimental study on the effects of atorvastatin in myocardial fibrosis and its effective machanisms
10.13699/j.cnki.1001-6821.2014.07.011
- VernacularTitle:阿托伐他汀对心肌纤维化影响的实验研究及其作用机制
- Author:
Rui-Fang LI
1
;
Wei-Jin FANG
;
Shan-Shan CAO
;
Ying SONG
;
Yan LI
;
Jian-Gang WANG
;
Xue-Ting LUO
;
Zhe-Zhen SUN
Author Information
1. 河南科技大学 医学院 药理学与分子生物学重点实验室
- Keywords:
renovascular hypertension;
myocardial fibrosis;
NAD ( P ) H oxidases;
connective tissue growth factor;
atorvastatin
- From:
The Chinese Journal of Clinical Pharmacology
2014;(7):594-596,606
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of the atorvastatin in the myocardial fibrosis and study the relationship of Nox 4 and connective tis-sue growth factor ( CTGF ) .Methods The two -kidney two -clip (2K2C) method was used to induce renovascular hypertension.After ator-vastatin (10, 5 mg· kg-1 · d-1 ) and candesartan (10 mg· kg -1 · d-1 ) were given for 4 weeks, hemodynamic parameters were measured and left ventricular weight to body weight ( LVW/BW) ratio was calculated.Mor-phological analysis was performed by using Masson staining.Western -blot was used to investigate the expression of Nox 4 , transforming growth factor(TGF) -β1 and CTGF in left ventricle ( LV).Results Aortic systolic pressure ( AoSP) ,aortic diastolic pressure ( AoDP) ,left ventricu-lar end-systolic pressure (LVESP),left ventricular end-diastolic pres-sure ( LVEDP) and LVW/BW ratio were markedly elevated while maxi-mum ascending rate of left ventricular pressure (+dp/dtmax ) and maxi-mum declining rate of left ventricular ( -dp/dtmax ) were significantly decreased in 2K2C rats.Atorvastatin or candesartan could prevente the decrease in +dp/dtmax or -dp/dtmax, however, atorvastatin had no significant blood -lowing effects.LVW/BW ratio and left ventricular perivascular collagen fraction ( PCVF ) increased significantly in hyper-tension rats.Both atorvastatin and candesartan partly reversed these effects and improved the cardiac hypertrophy and fibrosis.The expressionof Nox4, TGF-β1 and CTGF increased significantly in LV of 2K2C rats while their levels were down -regulated with drugs given.Conclusion The Nox4 involves in myocardial fibrosis regulated by TGF -β1 and CTGF in renovascular hypertensive rats.Atorvastatin may attenuate myocardial fibrosis of 2K2C rats and improve their cardiac function , the inhibition of TGF-β1/Nox4/CTGF pathway possibly contributes to these effects.
