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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 evaluate the protective effect of trimetazidine TMZ on right heart failure induced by pulmonary embolism and its effect on the expression of MMP-2, MMP-9 and TIMP-1 mRNA in right ventricle. Methods: Male Wistar rats were randomly divided into three groups: right femoral head failure group (RHF) left femoral vein injection of 1% vitreous microparticles 3 ml / 100 g; normal saline injection as control group (CON); trimetazidine Triazine treatment group (TMZ) was given TMZ 10 mg / kg / day after pulmonary embolism. After 6 weeks, rats in each group were subjected to transthoracic echocardiography to evaluate the right ventricular function, pathological examination was performed, and the expression of MMP-2, MMP-9, TIMP-1 mRNA in right ventricle was detected by RT-PCR. Results: In the RHF group, the right ventricular diameter was enlarged with tricuspid regurgitation and the peak systolic displacement of tricuspid annulus was reduced (TAPSE). The right ventricular fibrosis was increased by Masson staining. The expression of MMP-2, The mRNA expression of MMP-9 and TIMP-1 in TMZ group was significantly increased. After TMZ treatment, the diameter of right ventricle decreased and TAPSE increased while the expression of MMP-2, MMP-9 and TIMP-1 mRNA decreased. Conclusion: Trimetazidine can inhibit right ventricular fibrosis and improve right ventricular function, which may be related to the regulation of MMP-2, MMP-9 and TIMP-1 expression.