辛伐他汀对大鼠心肌梗死后血清TNF-α水平及心室肌间质胶原的影响

目的观察辛伐他汀对心肌梗死后大鼠血流动力学及心室肌Ⅰ、Ⅲ型胶原含量变化和血清肿瘤坏死因子-α（TNF-α）水平的影响。方法通过结扎冠状动脉前降支诱导大鼠急性心肌梗死（AMI）模型,模型建立后24h存活的30只大鼠随机分为AMI组（A组）和辛伐他汀组（S组）,每组15只;另设假手术组（C组）（n=10）,手术方法同模型组,但不结扎冠状动脉。建模后24h灌胃给药,A组及C组予生理盐水灌胃,S组予辛伐他汀20mg·kg-1·d-1灌胃,至术后8周。术后8周测定血流动力学参数〔心率、左室收缩压（LVSP）、左室舒张末压（LVEDP）、左室内压上升与下降速率（±dp/dt）及校正的速率（±dp/dt/LVSP）〕和血清TNF-α水平（ELLSA法）;取心脏标本测定左室相对质量〔左室质量（LVW）/体质量（BW）〕;心肌梗死面积及非梗死区Ⅰ、Ⅲ型胶原含量。结果与A组比较,S组心肌梗死面积、左心室截面直径、面积和左心室容积差异均无统计学意义（P均〉0.05）;LVW、LVW/BW和LVEDP均显著降低（P〈0.01或P〈0.05）,±dp/dt/LVSP绝对值升高（P〈0.05或P〈0.01）。与A组相比,S组左心室非梗死区Ⅰ型和Ⅲ型胶原含量和血清TNF-α水平显著减少（P均〈0.05）。左心室非梗死区Ⅰ型、Ⅲ型胶原含量和血清TNF-α水平均呈显著正相关（r分别为0.56和0.71,P均〈0.01）。结论辛伐他汀能有效抑制AMI左心室非梗死区Ⅰ、Ⅲ型胶原的产生以及缓解大鼠AMI后心室重构、改善心功能,这种作用可能与抑制体内TNF-α的水平有关。

Effects of simvastatin on serum TNF-a level and myocardial interststitial collagen content after myocardial in farction inrats

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.