缺血对大鼠心肌组织心型脂肪酸结合蛋白表达的影响

Effect of Ischemia on the Expression of Heart Type Fatty Acid Binding Protein in Rat Heart

目的观察大鼠心肌缺血对心肌组织心型脂肪酸结合蛋白(H-FABP)表达水平的影响并探讨其分子机制。方法 SD大鼠随机分为假手术组和心肌缺血1、3、7天组。采用左冠状动脉前降支结扎术构建大鼠心肌缺血模型,采用Power Lab检测心脏血流动力学参数左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)和左心室等容收缩期室内压上升最大速率(+dp/dt_(max))、左心室等容舒张期室内压下降最大速率(-dp/dt_(max))以评估心肌功能。分别采用定量PCR和免疫印迹检测心肌组织中H-FABP mRNA和蛋白质的表达及转录因子过氧化物酶体增殖物激活受体α(PPARα)的表达和磷酸化。观察大鼠存活率。结果与假手术组相比,大鼠心肌缺血后1、3和7天血流动力学参数LVSP、+dp/dt_(max)、-dp/dt_(max)持续降低,LVEDP持续上升(P<0.01)。定量PCR和免疫印迹显示心肌组织H-FABP在缺血后1天显著升高,缺血后3天回落,7天下降至基线水平。PPARα表达在缺血后持续降低,但其磷酸化水平在缺血后第1天增加,随后降低。心肌缺血组大鼠死亡率显著升高。结论心肌缺血早期,PPARα磷酸化增强而诱导H-FABP表达;随后由于损伤因素的持续存在,PPARα表达及磷酸化水平降低而下调H-FABP表达。

Aim To observe the effect of myocardial ischemia on the expression of heart type fatty acid binding protein( H-FABP) in myocardium of rats and to explore its possible molecular mechanism. Methods SD rats were randomly divided into sham operation group and myocardial ischemia 1,3,and 7 days groups. A model of myocardial ischemia was constructed by ligating the left anterior descending coronary artery. The heart function was assessed by detecting the cardiac hemodynamic parameters left ventricular systolic pressure( LVSP),left ventricular end-diastolic pressure( LVEDP)and + dp / dt_(max),- dp/dt_(max)using Power Lab instrument. The mRNA and protein expressions of H-FABP and peroxisome proliferator-activated receptor ɑ( PPARɑ) in myocardium were detected by quantitative PCR and Western blot respectively.The survival rate of rats was observed. Results Compared with the sham operation group,hemodynamic parameters LVSP,+ dp / dt_(max),- dp/dt_(max)were decreased and LVEDP was increased continuously at 1,3 and 7 days after myocardial ischemia( P < 0. 01). Results from quantitative PCR and Western blot showed that the expression of H-FABP was up-regulated at the 1 day after ischemia,but started to fall at 3 days and returned to the baseline level at 7 days after ischemia. The expression of PPARα was continuously decreased at 1,3 and 7 days after ischemia,however,its phosphorylation was increased at 1 day and then fell subsequently. The survival rate of myocardial ischemia group was decreased significantly compared with the sham operation group. Conclusions The expression of H-FABP in ischemic myocardium is elevated at the earlier stage,which is related to the increased phosphorylation of PPARα. Then,the expression of H-FABP is decreased,which may be related to the down-regulation of the expression and phosphorylation of PPARɑ.