Effects of simvastatin on serum TNF-α level and myocardial interststitial collagen content after myocardial infarction in rats

Objective To observe the effects of simvastatin on hemodynamics,serum tumor necrosis factor-alpha (TNF-α) level and the content of typeⅠand Ⅲ collagen of ventricular myocardium after myocardial infarction in rats.Methods The model of acute myocardial infarction (AMI) was established by ligating the anterior descending branch of left coronary artery in SD rats.Twenty four hours after the procedure,the surviving rats were randomly divided into AMI group (group A) and simvastatin group (group S) (n=15 each),and 10 rats received the same procedure without ligation were selected as control group (group C).After constructing,all experimental rats were administered by perfusing stomach of normal saline (group A and C) or simvastatin (20 mg·kg-1·d-1) (group S) from 24 hours after constructing model till 8 weeks after operation.The hemodynamic parameters including heart rate,systolic pressure in left ventricle (LVSP),left ventricular end-diastolic pressure (LVEDP),the up-and down-sloping speed (± dp/dt) and ± dp/dt of adjustment (± dp/dt/LVSP) and the level of serum TNF-α were determined at 8 weeks post operation.Then,the rats were killed,and the heart samples were taken for determining the left ventricular relative weight〔left ventricular weight (LVW) /body weight (BW) 〕,section diameter and section area of left ventricle and the contents of typeⅠand Ⅲ collagen of myocardium in non-infarcted zone.Results There were no significant difference in infarction size,the section diameter and area of left ventricle and left ventricular volume between the group A and S (all P 0.05).Compared with group A,LVW,LVW/BW and LVEDP were significantly decreased in group S (P 0.05 or P 0.01),and the absolute value of ± dp/dt/LVSP were significantly increased (P 0.05 or P 0.01) in group S.Compared with group A,the contents of typeⅠ and Ⅲmyocardial collagen of in the non-infarcted zone and serum TNF-α level were all significantly decreased (all P 0.05) in group S.Both the contents of typeⅠand Ⅲ collagen in the non-infarcted zone were positively correlated with serum TNF-α level (r=0.56 and 0.71 respectively,all P 0.01).Conclusions Simvastatin could effectively inhibit the generation of typeⅠand Ⅲ collagen in the non-infarcted zone and attenuate ventricular remodeling after AMI,and therefore improve cardiac function in rats.Inhibiting TNF-α level might to be involved in aforementioned effects.