曲美他嗪对肺动脉栓塞所致右心衰竭的保护作用

Role of Trimetazidine in a Pulmonary Artery Embolism Induced Right Heart Failure

目的:评价曲美他嗪(Trimetazidine TMZ)对肺动脉栓塞所致右心衰竭的保护作用,及其对MMP-2,MMP-9和TIMP-1mRNA在右心室中表达的影响。方法:雄性wistar大鼠随机分为三组:右心衰竭组(RHF)左侧股静脉注射1%玻球微粒3 ml/100 g;等量生理盐水注射为对照组(CON);曲美他嗪治疗组(TMZ)为肺动脉栓塞后给TMZ10 mg/kg/天。6周后各组大鼠首先进行经胸超声评价右心功能后取材进行病理学检测,以及RT-PCR检测右心室MMP-2,MMP-9,TIMP-1 mRNA表达水平。结果:RHF组大鼠超声检测发现右心室内径扩大并伴有三尖瓣反流,三尖瓣环收缩期峰值位移下降(TAPSE);Masson染色显示右心室纤维化增加;RTPCR结果显示MMP-2,MMP-9和TIMP-1mRNA表达水平明显升高;经TMZ治疗组大鼠右心室内径减小,TAPSE增加,而MMP-2,MMP-9和TIMP-1mRNA表达水平下降。结论:曲美他嗪能够抑制右心室纤维化,改善右心功能,可能与调节MMP-2,MMP-9和TIMP-1表达水平有关。

Objective： To investigate the effect of Trimetazidine, on MMP-2, MMP-9 and TIMP-1 mRNA expression in righ ventricle of PE-indueed right heart failure （RHF） rats. Methods： Wistar rats were injected 3ml/100g of 1% glass microspheres suspension （10-30μ m） or saline into left femoral vein. Rats were administered of Trimetazidine or saline at 10 mg/kg/day subcutaneously for six weeks. Eight rats of each group underwent transthoracic echocardiograph and morphological examination after six weeks. The right ventricular MMP-2, MMP-9, TIMP-1 mRNA expression were determined by reverse transcription polymerase chain reaction （RT-PCR）. Results： Transthoracic echocardiograph showed RHF group rats had tricuspid regurgitation and dilation of the right ventricle （P〈0.05）, which was normalized by TMZ （P〈0.05）. Right ventricle weight, right heart ratio （RV/LV＋Septum）, increased from control with RHF and was reduced with TMZ （P〈0.05）. Histological analysis cardiomyocyte fibrosis in RHF group and were attenuated by TMZ. Right ventricular myocardial MMP-2, MMP-9, TIMP-1 mRNA expression increased significantly in RHF group and TMZ inhibited them. Conclusions： This study indicates that TMZ could improve the right ventricular function, inhibit fibrosis. The function of TMZ may be connected with the regulation ofMMP-2, MMP-9 and TIMP-1.