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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。
Objective To observe the effects of simvastatin on the changes of hemodynamics, the changes of collagen type Ⅰ and Ⅲ and the level of serum tumor necrosis factor-α (TNF-α) in rats after myocardial infarction. Methods Acute myocardial infarction (AMI) model was induced by ligation of the anterior descending coronary artery in rats. Thirty rats survived 24 h after model establishment were randomly divided into AMI group (group A) and simvastatin group (group S) 15 rats in each group. Another sham operation group (C group) (n = 10) was used. The operation method was the same as the model group, but the coronary artery was not ligated. The rats were intragastrically administrated 24 hours after modeling. Rats in group A and group C were given normal saline, while in group S, simvastatin 20 mg · kg-1 · d-1 was intragastrically administered to 8 weeks after operation. At 8 weeks after operation, hemodynamic parameters (heart rate, LVSP, LVEDP, ± dp / dt and ± dp / dt / LVSP) and serum TNF-α levels (ELLSA method). Left ventricular relative mass (LVW / BW) was measured in heart specimens; myocardial infarct size and non-infarct areas Ⅰ, Ⅲ Collagen content. Results Compared with group A, there were no significant differences in myocardial infarct size, diameter of left ventricle, area and left ventricular volume in group S (all P> 0.05); LVW, LVW / BW and LVEDP were significantly decreased P <0.05), absolute value of ± dp / dt / LVSP increased (P <0.05 or P <0.01). Compared with group A, the content of type Ⅰ and type Ⅲ collagen and the level of serum TNF-α in group S were significantly decreased (all P <0.05). There was a significant positive correlation between the level of type Ⅰ and type Ⅲ collagen and the level of serum TNF-α in the left ventricular non-infarcted area (r = 0.56 and 0.71, respectively, P <0.01). Conclusion Simvastatin can effectively inhibit the production of type I and type III collagen in AMI non-infarcted area and relieve ventricular remodeling and improve cardiac function after AMI in rats, which may be related to the inhibition of TNF-α in vivo.