TNFα在大鼠心肌梗死后心室重构进程中表达的变化及意义

Tumor necrosis factor alpha expression during progression of left ventricular remodeling in rat myocardial infarction model

目的:探讨大鼠心肌梗死(MI)后心室重构进程中TNFα表达的改变及其与心功能的相关性。方法:雄性SD大鼠随机分为假手术和手术组(结扎大鼠冠状动脉前降支制作MI模型),每组再进一步分为1、7、14、284、2 d亚组。应用心脏超声和血流动力学测定心功能和心室重构;RT-PCR检测TNFα的表达。结果:手术组大鼠术后14 d起左室舒张末期直径(LVEDD)逐渐增加、左室射血分数(LVEF)及左室短轴缩短率(FS)逐渐降低,至42 d最明显,术后1 d起左室舒张末压(LVEDP)逐渐升高、左室压力上升最大速率(dp/dtmax)及压力下降最大速率(dp/dtmin)逐渐下降,以术后42 d最明显;MI后1 d TNFα即表达,7 d表达达高峰,其后逐渐下降,与相应假手术亚组比较有显著差异(P均<0.01)。TNFα的表达与LVEDD呈正相关(r=0.94,P<0.01),与FS、LVEF、dp/dtmax、dp/dtmin呈负相关(r=-0.91、-0.89、-0.80、-0.85,P均<0.05)。结论:大鼠MI后心室重构进程中TNFα表达呈动态改变并与心功能、心室重构相关,TNFα在促进心室重构、心功能异常中起重要作用。

Objective： To investigate the changes of tumor necrosis factor α（TNFα） expression and the relationship between TNFα and cardiac function during the progression of left ventricular remodeling in an experimental model of rat myocardial infarction（MI）. Methods： Ninety male Sprague Dawley rats were randomly divided into sham-operated and MI groups. Rats in MI group were induced by ligation of the anterior descending coronary artery and were subdivided into 1d, 7d, 14d, 28d and 42d groups. Sham-operated animals underwent the same surgical procedure without ligation. Heart function and left ventricular remodeling were studied by echocardiography and hemodynamics. The expression of TNFα mRNA was assessed by reverse transcription-polymerase chain reaction. Results： From day 14 after operation,left ventricular end-diastolic diameter（LVEDD） began to increase in MI group,and fractional shortening（FS） and left ventricular ejection fraction（LVEF） began to decrease; both the increase and decrease reached the maximal on day 42 after operation. From day 1 after operation,left ventricular end-diastolic pressure（LVEDP） began to increase, and left ventricular（LV） pressure maximal rate of rise and fall （dp/dtmax and dp/dtmin） began to decrease; both increase and decrease reached the maximal on day 42 after operation. TNFα began to express on day 1 after MI, reached peak on day 7, and began to decrease thereafter; there was significant differences between MI group and sham-operated group. The expression of TNFa was positively correlated with LVEDD（r=0.94, P〈0.01） and negatively with FS, LVEF,dp/dtmax and dp/dtmin（ r=-0.91, -0.89,-0.800 and -0.85, respectively, P〈0.05 ）. Conclusion： TNFα expression is associated with ventricular remodeling and cardiac function during the progression of left ventricular remodeling in rat MI model. TNFα may play an important role in promoting ventricular remodeling and heart dysfunction.