益气活血健脾化痰法调脂疗效观察及其与apoE基因多态性关系的临床研究

【作者】 梁晋普；

【导师】 郭维琴；

【作者基本信息】 北京中医药大学 ， 中医内科临床， 2006， 博士

【摘要】 目的1.观察益气活血、健脾化痰法指导下的调脂通脉颗粒对高脂血症气虚痰瘀证的调脂疗效。2.应用PCR-RLFP技术,研究高脂血症气虚痰瘀证人群apoE基因型与等位基因频率分布特征,并分析apoE基因多态性对研究人群脂质代谢的影响。3.在此基础上,进一步深入探究apoE基因多态性对益气活血、健脾化痰法调脂疗效的影响,以探讨遗传基因与药物疗效的关系。方法:检测118例高脂血症气虚痰瘀证患者apoE基因分型,按照频数计数法计算基因频率;对入组患者按随机、双盲、双模拟、阳性药物平行对照的原则,进行疗程为8周的临床试验观察,试验组64例,给予调脂通脉颗粒(太子参、茯苓、陈皮、水蛭、丹参、泽泻等),一次1袋,一日2次口服;及血脂康胶囊安慰剂,一次2粒,一日2次口服。对照组54例,给予血脂康胶囊,一次2粒,一日2次口服,及调脂通脉颗粒安慰剂,一次1袋,一日2次口服。比较观察治疗前后TC、LDL-C、TG、HDL-C、apoA1、apoB、LP(a)、AI以及中医证候的变化。观察两组部分患者治疗前后血流变学变化。结果:1.试验组调脂总有效率84.3%,有效降低血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、载脂蛋白B(apoB)以及动脉粥样硬化指数(AI),并且升高高密度脂蛋白胆固醇(HDL-C)(p﹤0.05),与治疗前比较差异显著;对照组调脂总有效率86.5 %,有明显降低TC、TG、LDL-C、apoB、AI,升高HDL-C作用(p﹤0.05);试验组与对照组比较,TC、TG、apoB、AI、HDL-C的变化,差异无统计学意义。在降低LDL-C方面,血脂康组优于调脂通脉颗粒组,从总体上,调脂通脉颗粒调脂疗效与血脂康相当,并且都具有良好的降低动脉粥样硬化指数作用。另外两组都能明显改善血液流变学指标,从而改善高脂血症粘、浓、聚的状态,疗效相当。治疗后试验组中医证候总积分明显低于对照组,(p﹤0.05)有显著性差异,调脂通脉颗粒改善中医证候明显优于血脂康,尤其在气虚血瘀症状方面的改善,(p﹤0.05),调脂通脉颗粒有明显优势。2.在118例高脂血症气虚痰瘀证人群中,共检测到4种基因型,以ε3等位基因频率最高,为89.4%,其中各基因型频率分布分别是:E2/3为8.5%,E3/3为78%,E2/4为1.7%,E3/4为11.9%,apoE基因型与等位基因频率分布,与北京自然健康人群比较,差异无统计学意义。3.apoE各基因型TC、LDL-C、apoB水平由高到低依次为E3/4﹥E3/3﹥E2/3,E3/4有明显升高TC、LDL-C、apoB的作用(p﹤0.05)。E3/4基因型HDL-C的水平在三种基因型中最低, E3/3比较,差异有统计学意义。结果还显示E3/4基因型的中医痰浊证积分明显高于E2/3、E3/3,差异有统计学意义(p﹤0.05),E3/4的气虚证候积分最高,但与E2/3、E3/3比较,差异无统计学意义。apoE基因多态性不影响TG、apoA1及LP(a)更多还原

【Abstract】 Objective:1.To observe the serum-lipid effect of TIAOZHI TONGMAI granule directed by method of YIQI HUOXUE HUATAN.2.Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to study the genotypes and allelic frequencies of QIXU TANYU syndrome population in hyperlipidemia, at the same time, analysis the effect of ApoE gene polymorphism on serum lipid.3.Furthermore to ascertain the effect of gene polymorphism on the method of YIHUOHUOXUE JIANPIHUATAN and the relationship between gene and drug effect.Method: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect apoE genotype in 118 hyperlipidemia patients, according to random, double blind, double imitate and control principle, the course of treatment is 8 weeks. Experimental group has 64 patients, giving TIAOZHI TONGMAI granule, 1 big, bid, po, XUEZHIKANG placebo 2 grain, bid, po. Control group has 54 patients, giving XUEZHIKANG capsule 2 grain, bid, po, TIAOZHI TONGMAI granule placebo 1 bag, bid po. To observe the change of TC、LDL-C、TG、HDL-C、apoA1、apoB、LP(a)、AI , TCM syndrome and blood flow between pretreatment and posttreatment.Result:1.The total effective rate in regulating serum lipid of experimental group is 84.3%,decreacing TC、LDL-C、TG、apoB、AI, increasing HDL-C)(p﹤0.05), there are significant difference comparing to pretreatment. The total effective rate in regulating serum lipid of control group is 86.5 %, decreasing TC、TG、LDL-C、apoB、AI, increasing HDL-C)(p﹤0.05), there are no difference between experimental and control group. XUEAHIKANG group is better than TIAOZHITONGMAI granule group in lowing LDL-C. The effect on regulating serum lipid of TIAOZHITONGMAI granule is correspond to XUEZHIKANG, furthermore it can resist atherosclerosis. Tow groups can improve blood flow index, the station of increasing mocusity, thick and assemble in hyperlipidemia. TIAOZHITONGMAI granule is superior to XUEZHIKANG in improving TCM syndrome.2.Four genotypes are found in 118 patients,ε3 is the highest accounting for 65. 6%.The frequency of E2/3,E3/3,E2/4, E3/ are 8.5%,78%,1.7%and 11.9% respectively .There are not significant difference between men and women . Compared with Beijing natural population, the genotypes and allelic frequencies更多还原