摘要
目的 研究替米沙坦对猪心动过速性心肌病(tachycardiomyopathy,TCM)心肌细胞Fas/FasL、Fas相关死亡结构域(Fas-associated death domain,FADD)、Bcl-2/Bax、caspase-3蛋白的影响,探讨替米沙坦对心肌细胞的保护作用及其作用机制.方法 18头家猪随机分为3组(每组n=6):快速右心房起搏组(TCM组),实验猪植入永久起搏器,起搏频率500次/min;快速右心房起搏加替米沙坦组(TCM+TS组),起搏器植入前3天至起搏2周后,每日给予替米沙坦(1.5 mg·kg-1·d-1)混于饲料中喂服;对照组,实验猪未植入起搏器也未服药.每周记录1次心电图,实验前后经胸心脏超声观测猪左心室舒张末期内径(LVEDD)和左心室射血分数(LVEF).2周后处死动物,取左心室组织,Western blot技术检测Fas/FasL、FADD、Bcl-2/Bax、caspase-3蛋白含量,逆转录聚合酶链反应(RT-PCR)检测fas、caspase-3 mRNA转录水平.结果 TCM组较对照组左心室心肌细胞Fas/FasL、FADD、Bcl-2/Bax、caspase-3蛋白表达量均明显增高(P〈0.05),TCM+TS组较TCM组Fas/FasL、FADD、Bcl-2/Bax、caspase-3蛋白表达量均明显降低(P〈0.05).TCM组较对照组左心室心肌细胞fas及caspase-3 mRNA表达明显增高(P〈0.05),TCM+TS组较TCM组fas及caspase-3 mRNA表达明显降低(P〈0.05).Fas与caspase-3蛋白表达呈明显正相关(r=0.987,P〈0.01);fas与caspase-3 mRNA表达呈明显正相关(r=0.950,P〈0.01).结论 替米沙坦通过抑制Fas/FasL通路相关蛋白的表达,进而减少细胞凋亡,延缓TCM病情进展.
Objective To investigate the effect of telmisartan on Fas/FasL, Fas - associated death domain (FADD) , Bcl- 2/Bax, and caspase- 3 in cardiomyocytes of porcine tachycardiomyopathy (TCM) model and to expound the protective effect and mechanism of telmisartan in cardiomyocytes. Methods Eighteen healthy pigs were ran- domly divided into 3 groups (n = 6 each). Rapid right atrial pacing group (TCM group) : permanent pacemaker was im- planted into experimental pigs, and pacemaker electrodes were imbedded into right anricle of pigs through vena jugularis interna (pacing frequency at 500 times/rain ). Rapid right atrial pacing and telmisartan treating group (TCM + TS group) : pacemaker was implanted as TCM group, telmisartan ( 1.5 mg ~ kg - l . d - 1 ) mixed with daily forage was fed to the animals beginning 3 days before implantation and continued until day 14 after implantation. Control group: neither pacemaker was implanted nor telmisartan was administered. Electrocardiogram (ECG) examination was implemented to each animal, left ventricular end - diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were meas- ured using transthoracic echocardiography at the beginning and end of experiment. At day 14 after implantation, animals were euthanized and tissues of left ventricle were harvested. The contents of Fas/FasL, FADD, Bcl - 2/Bax, and caspase - 3 were detected by Western blot. The expression of fas and capase - 3 mRNA was detected using reverse tran- scription polymerase chain reaction (RT - PCR) method. Results The expression of the protein of Fas/FasL, FADD,Bel - 2/Bax, and caspase - 3 in cardiomyocytes of left ventricle raised obviously in TCM group compared to control group (P 〈0.05 ). The expression of the protein of Fas/FasL FADD, Bel - 2/Bax, and easpase - 3 in eadiomyoeytes of left ventricle decreased obviously in TCM + TS group compared to TCM group ( P 〈 0.05). The expression of the mRNA of Fas and caspase -3 in eardiomyoeytes of left ventricle raised obviously in TCM group eompared to control group (P 〈 0.05 ). The expression of the mRNA of Fas and caspase - 3 in cadiomyocytes of left ventricle decreased obviously in TCM + TS group compared to TCM group ( P 〈 O. 05 ). Correlated statistics datas showed that the expression of the protein of Fas and easpase - 3 was positively con'elated (r = 0. 987, P 〈 0.01 ). The expression of the m]]NA of Fas and caspase - 3 was positively correlated (r = 0. 950, P 〈 0.01 ). Conclusion Telmisartan can postpone TCM progression by decrea- sing apoptosis of cardiomyocytes through suppression of Fas/FasL pathway.
出处
《徐州医学院学报》
CAS
2012年第2期74-78,共5页
Acta Academiae Medicinae Xuzhou
基金
江苏省科教兴卫工程项目(RC2007089)