【作者】 王东生；

【导师】 袁肇凯；

【作者基本信息】 湖南中医学院 ， 中医诊断学， 2002， 博士

【摘要】 目的： 1．阐明AS临床证型分布特点。 2．阐明AS痰瘀病理演变规律。 3．阐明AS痰瘀病理的形成机理。 方法： 1．文献研究：系统研究古今有关文献，归纳总结研究背景。 2．AS临床流行病学调查：采用多中心，大样本临床调查。 3．AS“痰瘀”病理相关指标检测：开展血脂、血糖、血胰岛素、胰岛素敏感指数、血流流变学及光镜、电镜等组织学检测。 4．AS“痰瘀”病理相关机理研究：运用免疫组化法检测主动脉组织细胞凋亡、肌动蛋白信号传导，运用RT-PCR法检测相关基因表达。 5．运用化痰活血法中药治疗AS大鼠，检测上述指标，反证AS“痰瘀”病理机制。 结果： 1．文献研究表明，动脉粥样硬化(AS)是一组以动脉非炎症性、退行性和增生性为特征的血管病变，其基本病机属本虚标实，本虚为气血阴阳亏虚，标实为痰凝、血瘀。其病理变化可概括为“因虚致实”，“因实致虚”的恶性循环而终致“本虚标实”的特征，病理关键为痰凝血瘀。 2．通过对AS最常见的疾病冠心病(CHD)310例流行病学调查，发现痰瘀相关证型占70.3％、心肾阳虚占8.4％、心肾阴虚占6.5％、寒滞心脉占5.2％、心气虚弱占9.7％；CHD痰凝心脉证的微观变化为血脂异常，痰瘀痹阻证的生化基础是血液流变学异常，及组织形态的改变；冠脉造影可见多支严重狭窄，粥样斑块明显，为CHD的重症。CHD由健康－＋非痰非瘀证一痰凝，C脉证一痰瘀痹阻证的变化中存在胰岛素抵抗现象；呈递进趋势；冠心病人外周血单个核细胞c－myc w、PDGF叭 WA表达量依次增加，＆“痰浊”贯穿于 C皿病理变化的始终。 3．动物实验证实了临床所见，表明AS大鼠由健康一非痰非瘀叶痰凝叶痰瘀痹阻的病理演变过程中，存在血脂、血液流变学异常和胰岛素抵抗现象，及相关基因 G、yC mRN、PDGF－A InRNA、G－fOSmRNA、bclZ mRNA表达异常增加，p53 mRNA表达降低，细胞凋亡、肌动蛋白表达均呈递进趋势。痰凝阶段主要是病理物质堆积的量变过程，痰瘀痹阻为相关细胞组织形态结构和功能改变的结果。 4．对AS大鼠进行中药干预，发现化痰活血法（养心通脉片）有较好疗效。（1）从整体水平看，能降低血脂，改善血液流变性，改变胰岛素低抗现象八2）从器官组织水平看，能保护动脉组织的结构及功能稳定性，对增生的斑块有消退和逆转作用。（3）从细胞水平看，能维护血管平滑肌细胞的结构与功能，使细胞凋亡趋于平衡。（4）从分子水平看，有改善AS相关基因C侧G、bGI2、p53、G－fOS、PDGF－A的异常表达，调整肌动蛋白的表达，使之趋向正常，从而达到保护心血管系统的作用。 结论： LAS临床证型以 “痰凝”气“血瘀”为主，“痰浊”贯穿于AS的始终。 2．“痰凝心脉”为AS关键病机，“痰瘀痹阻”是AS发展的必然趋势。 3．AS“痰瘀”病理的形成与脂质代谢异常、血液流变学异常、胰岛素敏感性指数降低、细胞凋亡异常、肌动蛋白表达增加、原癌基因C恻C、PDGFA、G－fos、bGI－2过量表达、时癌基因p53表达不足有关。 4．化痰活血法中药能有效的改善AS“痰瘀”病理。更多还原

【Abstract】 Objective:l.To expound the distribution of characteristics of clincal syndrome in atherosclerosis(AS).2.To expound the law of pathological development of the Syndrome of phlegm and bood stasis in As.3.To expound the mechanism of the syndrome of phlegm and blood stasis in AS.Methods:1.Literature research: To investigate systemicaly the related literature on As in ancieut and modern times and sum up its background.2.Epidemiology investigation on AS: To adopt the multicenter,maximus sample clinical survey.3.Related indexes of the syndrome of phlegm and blood stasis in As:blood lipid,blood sugar,insulin,insulin sensitive index,hemorheology, and optic, electron microscope,etc.4. Study on the related mechanism of the syndrome of phlegm and blood stasis in As:To detect the apoptosis and signal transmission of actin of aorta with immunocytochemistry and the related gene expression with RT-PCR.5.To treat As with traditional Chinese medicine of resolving phlegm and promoting blood circulation in rats,detect the indexes mentioned above ,and certificate the pathological mechanism of the syndrome of phlegm and blood stasis in As.Results:1 .Literature research showed As was non-inflammatorily ,regressively andhyperplasticaly pathological changes of artery. Its basic pathological mechanism was deficiency in origin which is deficiency of Qi,blood,ym and yang,and excess in superficiality which is accamulation of phlegm and blood stasis.Its pathological change was characterized with deficiency in origin and exces in superficiality caused by the vicious cycle of excess caused by deficiency and deficiency caused by excess.The pathological key was the accumulation of phlegm and blood stasis.2.Epidemiological research in 310 cases of coronary heart disease showed that the syndrom of phlegm and blood stasis occupied 70.3%,the syndrome of deficiency of Heart-Yang and kidney-yang 8.4%,the syndrome of deficiency of Heart-Yin and kindey-Yin 6.5%,the syndrome of obstruction of the heart collaterals and vessels due to 7.0%,respectively the microchange of the syndromes of obstruction of blood vessels due to accumulation of phlegm the abnormality of blood-Lipid.Biochemical change of the syndrome of obstruction of phlegm and blood stasis was the abnormality of hemorheology of phlegm and blood stasis was the abnormality of hemorheology associated with the alteration of tissue constructer,which had coronary shadow showed severe multi-ramus constriction and transparent atheromatous plaque,which were severe synptoms of CHD.There was insulin resistance in the process of changes from health to the syndrom of non-phlegm and non-blood stasis to the syndrome of obstrustion of blood vessel to the syndrome of obstructon of phlegm and blood stasis in CHD.The expression of c-myc mRNA,PDGF-AmRNA of blood corpulse in patients with coronary heart disease increased by tums,and the phlegm and blood stasis existed all through the pathological process of CHD.3.Animal experiment confirmed the clinical findings mentioned above.In addition,the expression of c-mycmRNA,PDGF-AmRNA,c-fosmRN/^, bcl-2mRNA increased abnormally and the expression of P53 mRNA decreased ,and the expression of actin and apoptosis increased step by step.The stage of phlegm and stasis was the quantitative change procedure of stack of pathological substances, and the obstraction of phlegm and blood stasis was caused by changes of associated cellular tissue constitution and function.4.The METhod of resolving phlegm and promoting blood circulation had a better effect on As with the traditional Chinese medicine.in rats(l)In whole level , it could decrease Lipid-blood,improve hemorheology,and alter insulin resistance.(2)In the organ and tissue level, it could protect the structure of arterial tissue,keep its function stabilized and fadeaway and reverse hyperplastic plaque of arterial tissue.(3)In the cell level,it could protect the structure and function of blood vessel smooth muscle cell, and keep apoptosis equilibrium.(4)In the molecular leve更多还原