替米沙坦对大鼠冠状动脉微栓形成后心肌细胞凋亡的影响

Influnence of Telmisartan on the Apoptosis of Rat Cardiomyocyte in Coronary Microthrombosis

目的:建立冠脉微血栓模型,观察冠脉微血栓后心肌细胞的凋亡和对心功能的影响,并观察替米沙坦对微血栓形成和心肌细胞凋亡的影响。方法:将SPF级SD大鼠冠状动脉注射月桂酸钠400μg后,随机分入微栓组和替米沙坦组(饮水中给药10mg·kg-1·d-1),对照组则以等量生理盐水替代月桂酸钠。术前和术后28d行超声心动图检查,术后行心肌TUNEL染色检测凋亡心肌细胞数。结果:在急性实验中与对照组相比微栓组和替米沙坦组冠脉内微血栓形成率、TnI值、心肌细胞凋亡率均显著增加(P<0.01),而微栓组与替米沙坦组之间差异无统计学意义(P>0.05)。在慢性实验中替米沙坦组较微栓组左室舒张末期内径(LVEDD)减小(P<0.01),左室射血分数(LVEF)增加(P<0.01);替米沙坦组心肌细胞凋亡率显著低于微栓组(P<0.01)。慢性实验中,冠状动脉微栓塞形成28d后,心肌细胞凋亡率与大鼠LVEDD和LVEF之间均呈明显正相关(均P<0.01)。结论:冠状动脉内注射月桂酸钠能够成功建立冠状动脉微血栓的模型;冠脉内微血栓增加心肌细胞的凋亡,是导致心功能下降的原因之一;替米沙坦能有效地抑制心脏重塑,改善心功能,并能抑制冠脉微血栓后心肌细胞的凋亡。

Objective： To establish a new type of coronary microthromboembolism model. To observe cardiomyocytes apoptosis and the changes of heart function,and to observe the effect of ARB on microthrombogenesis and apoptosis. Methods： In acute or chronic experiment,all SD rats were randomly divided into three groups which included microthromboembolism group with the injection of 400 μg sodium laurate into the coronary arteries of SD rats, TS group with drinking telmisartan （10 mg/kg）,and NS group with NS instead of sodium laurate. UCG was applied before and 28 d postoperatively. Cardiomyocyte apoptosis was detected by TUNEL staining. Results： cTnI concentration in blood, apoptosis rate of myocardial cells and the rate of microthromboembolism in microthromboembolism group and TS group were significantly higher than that in control group in acute experiment （P 〈 0.01 ）,and there was no significant difference between rnicrothromboembolism group and TS group （P 〉 0.05 ）. LVEDD in microthromboembolism group and TS group decreased compared to that in control group in chronic experiment （P 〈 0.01 ）,and LVEF increased than that in control group （P 〈 0.01 ）. Apoptosis rate of myocardial cells in TS group was lower than that in microthromboembolism group （P〈 0.01 ）. There was a positive correlation between Apoptosis rate of myocardial cells and LVEDD and LVEF 28 days after ism in chronic experiment （P 〈 0.01 ）. Conclusion： A coronary microthromboembolism model was successfully established by injecting sodium laurate into the coronary arteries. Coronary micro-thrombogenesis may promote the apoptosis of cardiomyocytes,and is one of the reason for heart function decrease. Telmisartan can efficiently suppress ventricles reconstruction, improve heart function, and inhibit the apoptosis of myocardial cells after microthrombogenesis in coronary artery.