阿托伐他汀及辅酶Q10对心衰过程中Fas/FasL系统的影响

Effect of Atrovastatin and Coenzyme Q10 on Fas/FasL System in Chronic Heart Failure

目的:探讨阿托伐他汀对慢性心力衰竭过程中Fas/FasL系统影响及联合辅酶Q10的作用。方法:采用阿霉素腹腔注射法复制大鼠心力衰竭模型(2.5 mg/kg,每周给药3次,给药2周),将30只Wistar大鼠分为空白组(6只)及心衰模型组(24只),给药完毕后观察2周,将心衰模型组大鼠随机均分为心衰组、阿托伐他汀治疗组[3.75 mg/(kg.d)]、辅酶Q10治疗组[2.8 mg/(kg.d)]、联合治疗组,连续灌胃2个月。超声检测大鼠心功能,免疫组化法检测心肌组织中Fas、FasL蛋白水平,并观察大鼠心肌细胞凋亡情况。结果:相较于空白组,其余各组均有不同程度的心功能减低,心肌细胞凋亡、Fas与FasL蛋白阳性表达增加,以心衰组最明显。相较于心衰组,3个治疗组凋亡细胞数目、Fas与FasL蛋白阳性表达细胞均降低,联合治疗组较单药治疗组进一步降低。结论:心衰大鼠心肌组织Fas、FasL蛋白表达、细胞凋亡均增加,Fas/FasL系统在心脏由代偿性心肌肥厚向心衰转变过程中起到重要作用。阿托伐他汀、辅酶Q10均可通过影响Fas/FasL系统、影响细胞凋亡而对心衰起到一定作用。

Objective： To investigate whether Atorvastatin influence the Fas/FasL system during the progress of chronic heart failure and the combining effect of coenzyme Q10 on the protective treatment.Methods： The model of chronic heart failure was created by injecting the Adriamycin（2.5 mg/kg,3 times per week for 2 weeks） in Wistar rats.Thirty rats were divided randomly into control group,heart failure group,Atorvastatin treatment group（3.75 mg/kg per day）,coenzyme Q10 treatment group（2.8 mg/kg per day）,and combined treatment group.The intragastric administration of Atorvastatin and（or） coenzyme Q was lasting for 2 months.After the treatment,LV performance was examined by echocardiography.Immunohistochemical staining were used to detect the changes of apoptosis and expression of Fas and FasL protein.Results： Few apoptotic myocardial cells were shown in control group,while apoptotic myocardial cells were found frequently both in heart failure group,Atorvastatin treatment group,coenzyme Q10 treat...更多ment group,and combined treatment group.The number of apoptotic myocardial cells in heart failure group increased significantly in comparison with that in the other three treatment groups（P〈0.05）.There was significant difference（P〈0.05） in apoptotic index（AI） between heart failure group and combined treatment group.When the chronic heart failure occurred,AI was increased very significantly in model group（P〈0.05） than those in treatment group.Conclusion： Increasing of myocardial apoptosis may be the important process during which the compensated hypertrophy is developing into heart failure.Changes of myocardial apoptosis and the expression of Fas and FasL genes suggest that apoptosis and Fas/FasL system are involved in the experimental congestive heart failure in rats.The combined treatment is better than the single ones.