通心络胶囊对不同载脂蛋白E基因冠状动脉粥样硬化性心脏病的影响

目的应用基因测序技术观察通心络胶囊对不同载脂蛋白E(ApoE)基因冠状动脉粥样硬化性心脏病(CHD)的治疗效果,并探究ApoE基因多态性与治疗前后CHD中医证型证候积分、血脂水平的相关性,为中医辨证施治CHD提供分子生物学依据。方法将118例CHD患者采用随机、对照、盲法试验设计,分为2组,对照组予单硝酸异山梨酯缓释片40mg,每日1次口服;酒石酸美托洛尔片25mg,每日2次口服;阿司匹林肠溶片25mg,每日1次口服;治疗组在对照组基础上同时予通心络胶囊3粒,每日3次口服。分别检测不同中医证型的ApoE基因多态性和治疗前后血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),统计证候积分,比较通心络胶囊对不同ApoE等位基因、不同ApoE基因表型、不同证型CHD的中医证候积分和血脂水平的差异及疗效。结果 2组中医证候总积分治疗前后比较差异有统计学意义(P0.05),治疗后中医证候总积分组间比较差异有统计学意义(P0.05)。2组ε2、ε3、ε4各等位基因治疗前后自身比较,气阴两虚证、痰阻心脉证、心血瘀阻证均有统计学意义(P0.05);治疗组ε4与ε2、ε3比较,痰阻心脉证积分降低改善率最高(P0.05),其他各基因表型间的气阴两虚证及心血瘀阻证改善率比较差异无统计学意义(P0.05),治疗组ε4型改善率痰阻心脉证疗效最好,优于ε2、ε3型;对照组各等位基因对于气阴两虚证、痰阻心脉证、心血瘀阻证积分改善率比较差异无统计学意义(P0.05)。2组组内各不同基因表型调脂疗效比较,TC、LDL-C降低和HDL-C升高的改善率比较差异有统计学意义(P0.05),TG降低的改善率比较差异无统计学意义(P0.05),2组组间各相同基因表型间治疗前后改善率比较差异无统计学意义(P0.05)。结论通心络胶囊干预CHD疗效显著,对不同ApoE基因CHD的不同中医证型的疗效均具有影响,但对气阴两虚证、痰阻心脉证、心血瘀阻证具有明显疗效,尤以痰阻心脉证疗效最为显著;可有效降低TC、LDL-C和升高HDL-C。

Effect of Tongxinluo capsule on CHD of different apolipoprotein e(ApoE) gene

Objective To observe the therapeutic effects of Tongxinluo capsule on CHD of different apolipoprotein e（ApoE）gene by applying the most advanced gene sequence testing technique,and to find the correlation between apolipoprotein e（ApoE）gene polymorphism and CHD Traditional Chinese Medicine pattern and blood-fat（before and after treatment）providing molecular biology evidences for CHD＇ treatment to differentiation of symptoms and signs of TCM.Methods 118 CHD patients were randomly divided into two groups by contrastion and blind trial.The patients in control group were treated with isosorbide mononitrate 40 mg,once a day,metoprolol tartrate 25mg,twice a day,aspirin enteric-coated tablets 25mg,once a day.While cases in the treatment group were treated on the base of control group with adding 3 Tongxinluo capsules,three times a day.Then respectively survey ApoE gene polymorphism of different traditional Chinese medicine syndromes,indexes（pre and post treatment）of TC,TG,HDL-C and LDL-C,to get the statistic analysis on difference and effect（intervened by Tongxinluo capsule）of different apolipoprotein e（ApoE）allele、gene phenotype and CHD traditional Chinese medicine pattern and level of blood-fat.Results Total integrals of both groups traditional Chinese medicine pattern had statistical difference between before and after treatment（P〈0.05）.There was statistical difference of intergroup comparison after treatment（P〈0.05）.ε2、ε3、ε4 allele respectively compared with themselves between before and after treatment,deficiency of both qi and yin,coagulation of phlegm and heart blood stagnation syndromes of both groups were statistical different（P〈0.05）.ε4 allele compared with ε2、ε3 allele in treatment group,the decline-improvement rate of integral of coagulation of phlegm syndrome was best（P〈0.05）.There weren＇t statistical differences of improvement of deficiency of both qi and yin and heart blood stagnation syndromes among all other gene phenotypes（P〉0.05）.Type ε4 in treatment group had the best effect of improving coagulation of phlegm syndrome,better than type ε2、ε3;while in control group,there were no significant differences of integral improvement of all the syndromes between each allele（P〉0.05）.For intergroup every different gene phenotype,comparison of effect of regulating lipid in both groups,differences were statistical significance in the decline of TC、LDL-C and increase of HDL-C（P〈0.05）,there wasn＇t significant difference in the decline of TG（P〉0.05）.But for intergroup comparison of every same gene phenotype in both groups,differences between before and after treatment weren＇t significant（P〉0.05）.Conclusion Tongxinluo capsule has definite effect on different syndromes of traditional Chinese medicine in different apolipoprotein e（ApoE）gene CHD,obviously on deficiency of both qi and yin、coagulation of phlegm and heart blood stagnation syndromes,but for coagulation of phlegm syndrome the effect is the best.There is obvious effect in the decline of TC,LDL-C and increase of HDL-C.