缺血性脑卒中痰瘀阻络证和肝风上扰证的生物学基础的研究
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摘要
目的缺血性脑卒中是由于脑动脉粥样硬化或血栓栓塞引起的最常见脑血管疾病,其高发病率、高死亡率及由此引起的瘫痪、失语及痴呆使患者的生存质量低下,已成为威胁我国人民健康的重大疾病。中医证候诊断的主观性较大,影响其证候诊断的稳定性及疗效的可重复性,很大程度上制约了中医药在缺血性脑卒中预防和治疗中的应用及推广。缺血性脑卒中具有的不同证型可能是由于遗传基础不同而导致引发缺血性脑卒中发病的病因病机不同,表现为各异的临床特征。因此,我们拟对中医辨证为风痰瘀血、痹阻脉络证及肝阳暴亢、风火上扰证之缺血性脑卒中患者及健康人β-纤维蛋白原-455G/A基因、血管紧张素转化酶基因ACE(I/D)、低密度脂蛋白受体(LDL-R)基因的多态性分布、临床表型特点进行相关性分析,研究不同中医证型缺血性脑卒中相关基因分布、疾病临床表型特征与中医证候之间的关系,从基因-疾病-证候相关角度揭示不同中医证型缺血性脑卒中的生物学基础及其发生的内在规律,初步揭示中医证候的现代医学生物学基础。
方法根据研究目的,本试验采用大样本、平行对照、多中心、横断面研究的试验方法。在湖北省中医院神经内科、武汉市第一医院神经内科、武汉大学附属中南医院神经内科共收集脑梗死患者410例,经筛选符合纳入标准并数据完整的有效病例为382例;共收集健康对照组200例。收集临床症状、体征及相关数据,采集血液样本,提取全血DNA,采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)的方法检测β-纤维蛋白原-455G/A基因、血管紧张素转化酶基因ACE(I/D)、低密度脂蛋白受体(LDL-R)基因多态性。分析缺血性脑卒中相关基因分布、疾病临床表型特征与中医证候之间的关系。
结果1.一般资料382例脑梗死组:男性206例,女性176例;平均年龄为67.8岁±13.1岁,40～49岁46例,50～59岁89例,60～69岁137例,70～79岁110例;病史中有高血压病者219例,风湿性心脏病者34例,冠心病者98例,糖尿病者113例,高血脂症206例,吸烟134例,饮酒78例,有脑血管病高危因素家族史261例;风痰瘀血、痹阻脉络证237例,肝阳暴亢、风火上扰证145例。健康对照组:男性107例,女性93例;平均年龄为63.7岁±14.5岁,40～49岁24例,50～59岁58例,60～69岁87例,70～79岁31例;病史中无高血压、冠心病、脑梗塞等心脑血管疾病,身体各系统未发现重大疾病,吸烟51例,饮酒37例,有脑血管病高危因素家族史84例。
2.缺血性脑卒中急性期肝阳暴亢,风火上扰证患者的收缩压和静息心率均明显高于风痰瘀血、痹阻脉络证患者,这与风火上扰,“火性炎上”的病机相一致。患者血常规中白细胞高于健康对照组,提示脑梗死急性期机体可能有炎症反应存在,这一结果与相关研究认为“近期感染是脑卒中的诱发因素”相类似,为中药解毒,现代医学抗炎、抗感染预防脑卒中提供思路。血脂增高是脑梗死发生的独立危险因素。LDL的增高与HDL的降低是风痰瘀血,痹阻脉络证区别于肝阳暴亢,风火上扰证的生化指标之一。血粘度的改变是脑梗死急性期病理因素之一,脑梗死急性期血粘度的改变与风痰瘀血,痹阻脉络证关系更密切,为临床运用活血化瘀药物改善循环提供理论依据。
3.在基因多态性研究中,B-纤维蛋白原A-455等位基因与脑梗死有关,这种相关性是相对于其他危险因素的一个独立危险因素。A-455等位基因与风痰瘀血、痹阻脉络证高度相关。A-455等位基因可能通过影响血浆纤维蛋白原的水平,调节血液流变,而在临床表现为痰瘀证候特征。因此,A等位基因可能是缺血性脑卒中风痰瘀血、痹阻脉络证的遗传易感因素。
4.在低密度脂蛋白受体LDL-R基因多态性研究中,我们发现风痰瘀血、痹阻脉络证患者的A+等位基因频率显著高于健康对照组和肝阳暴亢、风火上扰证。提示,A+等位基因与风痰瘀血、痹阻脉络证密切相关,是缺血性脑卒中患者表现风痰瘀血、痹阻脉络证候的遗传易感因素。同时,血浆TG、LDL的增高与风痰瘀血、痹阻脉络证密切相关,高TG、高LDL的患者临床多见风痰瘀血、痹阻脉络证候表现,这与血脂多属中医痰浊的学术观点不谋而合。而血浆HDL低水平与肝阳暴亢、风火上扰证密切相关,肝阳暴亢、风火上扰证患者的血浆HDL水平较风痰瘀血、痹阻脉络证患者和健康人群显著降低。以上结果提示,不同LDL-R基因类型可能通过影响血脂代谢而使缺血性脑卒中患者表现不同的临床证候类型,A+等位基因是缺血性脑卒中患者表现风痰瘀血、痹阻脉络证候的遗传易感因素。而不同的血脂也表现有不同的证候特征。血脂增高的临床表现与中医痰瘀实邪的临床表现密切相关。
5.在ACE-I/D基因多态性研究中,脑梗死组ACE-DD基因型和D等位基因频率均明显高于正常对照组(P＜0.05)。ACE-DD基因型或D等位基因可能在脑梗死中起作用,且与脑梗死肝阳暴亢、风火上扰证密切相关,可能是该证候的遗传易感因素。脑梗死组患者DD基因型患者血浆AngⅡ水平显著增高,且肝阳暴亢,风火上扰证患者增高更显著。DD基因型导致血浆AngⅡ水平增高可能是中医肝阳暴亢,风火上扰证的遗传易感因素。
结论与缺血性脑卒中相关的基因多态性可以通过影响相关临床表型的表达间接影响中医中风的临床证候,即:表现相同证候的不同患者可能存在有某种程度的遗传相似性,而遗传基因的不同可能是某些证候的遗传易感因素。LDL的增高与HDL的降低,血粘度的改变,A-455等位基因与风痰瘀血,痹阻脉络证关系密切,不同LDL-R基因类型可能通过影响血脂代谢而使缺血性脑卒中患者表现不同的临床证候类型,A+等位基因是缺血性脑卒中患者表现风痰瘀血、痹阻脉络证候的遗传易感因素。DD基因型导致血浆AngⅡ水平增高可能是中医肝阳暴亢,风火上扰证的遗传易感因素。
Objectives: Cerebral arterial thrombosis was most common disease because of cerebral atherosclerosis or thromboembolism, its high disease incidence rate, the high mortality rate that had caused the paralysis, the aphasia and the aphrenia and caused patient's survival quality to be low. The significant disease had threatened to our country people health. Traditional Chinese medicine syndrome of diagnosis has much subjectivity, which affects constancy of diagnosing syndrome and repeatability of curative effect. Different pattern syndrome of cerebral arterial thrombosis maybe had different etiological factor and pathogenesis because of the distinct hereditary basis, cerebral arterial thrombosis had vary clinical feature.
Therefore, we planed to traditional Chinese medicine differentiation of symptoms and signs cerebral arterial thrombosis patients pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti-vein and pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind. We carried the relevant analysis of the gene polymorphism distribution and the clinical phenotype characteristic on the patient and healthy people's genes ofβ- fibrinogen - 455G/A, angiotensin-convertion enzyme (ACE), low density lipoprotein acceptor (LDL-R).To research the relations of traditional Chinese medicine syndrome and related gene distribution, clinical phenotype characteristic of cerebral arterial thrombosis of different Chinese medicine syndrome, revealed biology foundation and inherent axiom of cerebral arterial thrombosis of different Chinese medicine syndrome from the gene - disease - syndrome point of view, preliminary revealed modern medicine biology foundation of traditional Chinese medicine syndrome. Methods: According to research purpose, this experiment adopted the large sample, the parallel comparison, multi-central, the cross section research testing method. In nerve internal medicine department of Hubei Province hospital of traditional Chinese medicine, Wuhan first hospital, ZHONG NAN hospital of Wuhan university, collected cerebral infarction patients altogether were 410 examples, after screening , consistent with standard and complete effective data of the cases were 382 examples; collected healthy control group 200 examples.
Collected the clinical symptoms, the objective sign and the correlation data; Collected blood sample, extract whole blood DNA; adopted polymerase chain reaction restrictive fragment length polymorphism (PCR-RFLP) method to examine the gene polymorphism ofβ-fibrinogen - 455G/A, angiotensin-convertion enzyme (ACE), low density lipoprotein acceptor (LDL-R). We analyzed the relations of related gene distribution, disease clinical phenotype characteristic and traditional Chinese medicine syndrome of cerebral arterial thrombosis.
Results: 1. the common data 382 examples of cerebral infarction group: Masculine 206 examples, feminine 176 examples; The average age is 67.8±13.1, 40-49 year old of 46 examples, 50-59 year old of 89 examples, 60-69 year old of 137 examples, 70-79 year old of 110 examples; In the medical history the data has the hypertension patient 219 examples, the rheumatic heart patient 34 examples, the coronary artery disease 98 examples, the diabetes patient 113 examples, the hyperlipemia 206 examples, smoke 134 examples, drink wine 78 examples, has the cerebrovascular disease high-risk factor family history 261 examples.
pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein 237 examples, pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind 145 examples. Healthy control group: Masculine 107 examples, feminine 93 examples; The average age is 63.7±14.5, 40-49 year old of 24 examples, 50-59 year old of 58 examples, 60-69 year old of 87 examples, 70-79 year old of 31 examples; In the medical history haven't heart cerebrovascular diseases and so on hypertension, coronary artery disease, cerebral infarction, bodily various systems has no significant disease, smoke 51 examples, drink wine 37 examples, has the cerebrovascular disease high-risk factor family history 84 examples.
2. hyperactivity of liver-YANG, febrile disease complicated by wind syndrome of patient's contractive pressure and resting heart rate obviously to be higher than the hyperactivity of liver-YANG, febrile disease complicated by wind syndrome of patient in the acute stage of cerebral arterial thrombosis, which coincidence with pathogenesis of febrile disease complicated by wind, "RE XING YAN SHANG". The number of white blood corpuscle of blood Routine in patients are higher than the healthy control group, which hint to be inflammatory reaction in the body of cerebral arterial thrombosis acute stage, this result is similar with related research of "the near future infect is the stroke causative factor", which provide the mentality of traditional Chinese medicine disintoxicating, modern medicine anti-inflammatory, anti-infection to obviate stroke. The raised blood-fat is the independence hazard factor of cerebral infarction. The high of LDL and the low of HDL are the one of biochemical indicators to distinguish pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein and pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind. The blood viscosity's change is one of factors of cerebral infarction acute stage, the blood viscosity's change in cerebral infarction acute stage has close relations with pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein, which provides the theory basis for improving circulation by using drug for invigorating blood circulation and eliminating stasis.
3. In the gene polymorphism research,β- fibrinogen A- 455 allele concerned with cerebral infarction, this kind of dependablity is an independent risk factor opposite to other danger factors. A-455 allele is highly related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. A-455 allele has phlegm stasis pattern syndrome characteristic in clinical manifestation, possibly through affects the level of blood plasma fibrinogen, and adjusts hemorheology. Therefore, A-455 allele possibly is the genetic predisposition symbol of pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein in cerebral arterial thrombosis.
4. In LDL-R gene polymorphism research, We discovered that the anemogenous phlegm stagnant blood, arthralgia spasm anti- vein pattern syndrome patient's A+ allele frequency obviously is higher than the healthy control group and pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind. Indicate that A+ allele is closely related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein, A+ allele is genetic predisposition factor of stroke patient's pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein.
At the same time, high blood TG and LDL is closely related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti-vein, high blood TG and LDL patient show pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein in clinical, which agree without prior consultation with academic viewpoint of blood-fat belonging to Chinese medicine phlegm muddy. But the low level of blood HDL is closely related to pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind, hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome of the patient's blood HDL level is obviously lower than anemogenous phlegm stagnant blood, arthralgia spasm anti-vein pattern syndrome of patient and the healthy crowd.
Above results prompt, the different LDL-R gene type possibly through affects the blood lipid metabolism to cause the stroke patient to display the different clinical pattern syndrome, A+ allele is genetic predisposition factor of stroke patient's pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. But the different level of blood lipid also displays the different syndrome characteristic. The clinical manifestation of rising blood lipid is close related to the clinical manifestation of Chinese medicine phlegm stasis solid evil. 5. In the ACE-I/D gene polymorphism research, the ACE-DD genotype and the D allele of cerebral infarction group frequency obviously are higher than the normal control group (P<0.05). ACE-DD genotype or D allele possibly has an effect in cerebral infarction, and is close related to cerebral infarction of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome, which possibly is the genetic predisposition symbol. DD genotype patients of the cerebral infarction group obviously has high level of blood Ang II, patients of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome has more higher level of blood Ang II.The DD genotype lead to the higher level of blood Angll,which possibly is the diagnosis genetic predisposition symbol of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome of traditional Chinese medicine.
Conclusion: Gene polymorphism related to cerebral arterial thrombosis may indirectly influence Chinese medicine pattern syndrome clinical of stroke through influence on the expression of clinical phenotype, Appearance the same syndrome of the different patients possibly exist some degree of heredity similarity, the different genetic gene may be genetic predisposition factor of some syndrome. Raised LDL, lowered HDL, the change of blood viscosity and A—455 allele are close related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. The different LDL-R gene type cause the stroke patient to different clinical syndrome possibly through influence the blood lipid metabolism, A+ allele is genetic predisposition factor of stroke patient's pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. The DD genotype lead to the higher level of blood Ang II, which possibly is the diagnosis genetic predisposition symbol of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome of traditional Chinese medicine.
方法根据研究目的,本试验采用大样本、平行对照、多中心、横断面研究的试验方法。在湖北省中医院神经内科、武汉市第一医院神经内科、武汉大学附属中南医院神经内科共收集脑梗死患者410例,经筛选符合纳入标准并数据完整的有效病例为382例;共收集健康对照组200例。收集临床症状、体征及相关数据,采集血液样本,提取全血DNA,采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)的方法检测β-纤维蛋白原-455G/A基因、血管紧张素转化酶基因ACE(I/D)、低密度脂蛋白受体(LDL-R)基因多态性。分析缺血性脑卒中相关基因分布、疾病临床表型特征与中医证候之间的关系。
结果1.一般资料382例脑梗死组:男性206例,女性176例;平均年龄为67.8岁±13.1岁,40～49岁46例,50～59岁89例,60～69岁137例,70～79岁110例;病史中有高血压病者219例,风湿性心脏病者34例,冠心病者98例,糖尿病者113例,高血脂症206例,吸烟134例,饮酒78例,有脑血管病高危因素家族史261例;风痰瘀血、痹阻脉络证237例,肝阳暴亢、风火上扰证145例。健康对照组:男性107例,女性93例;平均年龄为63.7岁±14.5岁,40～49岁24例,50～59岁58例,60～69岁87例,70～79岁31例;病史中无高血压、冠心病、脑梗塞等心脑血管疾病,身体各系统未发现重大疾病,吸烟51例,饮酒37例,有脑血管病高危因素家族史84例。
2.缺血性脑卒中急性期肝阳暴亢,风火上扰证患者的收缩压和静息心率均明显高于风痰瘀血、痹阻脉络证患者,这与风火上扰,“火性炎上”的病机相一致。患者血常规中白细胞高于健康对照组,提示脑梗死急性期机体可能有炎症反应存在,这一结果与相关研究认为“近期感染是脑卒中的诱发因素”相类似,为中药解毒,现代医学抗炎、抗感染预防脑卒中提供思路。血脂增高是脑梗死发生的独立危险因素。LDL的增高与HDL的降低是风痰瘀血,痹阻脉络证区别于肝阳暴亢,风火上扰证的生化指标之一。血粘度的改变是脑梗死急性期病理因素之一,脑梗死急性期血粘度的改变与风痰瘀血,痹阻脉络证关系更密切,为临床运用活血化瘀药物改善循环提供理论依据。
3.在基因多态性研究中,B-纤维蛋白原A-455等位基因与脑梗死有关,这种相关性是相对于其他危险因素的一个独立危险因素。A-455等位基因与风痰瘀血、痹阻脉络证高度相关。A-455等位基因可能通过影响血浆纤维蛋白原的水平,调节血液流变,而在临床表现为痰瘀证候特征。因此,A等位基因可能是缺血性脑卒中风痰瘀血、痹阻脉络证的遗传易感因素。
4.在低密度脂蛋白受体LDL-R基因多态性研究中,我们发现风痰瘀血、痹阻脉络证患者的A+等位基因频率显著高于健康对照组和肝阳暴亢、风火上扰证。提示,A+等位基因与风痰瘀血、痹阻脉络证密切相关,是缺血性脑卒中患者表现风痰瘀血、痹阻脉络证候的遗传易感因素。同时,血浆TG、LDL的增高与风痰瘀血、痹阻脉络证密切相关,高TG、高LDL的患者临床多见风痰瘀血、痹阻脉络证候表现,这与血脂多属中医痰浊的学术观点不谋而合。而血浆HDL低水平与肝阳暴亢、风火上扰证密切相关,肝阳暴亢、风火上扰证患者的血浆HDL水平较风痰瘀血、痹阻脉络证患者和健康人群显著降低。以上结果提示,不同LDL-R基因类型可能通过影响血脂代谢而使缺血性脑卒中患者表现不同的临床证候类型,A+等位基因是缺血性脑卒中患者表现风痰瘀血、痹阻脉络证候的遗传易感因素。而不同的血脂也表现有不同的证候特征。血脂增高的临床表现与中医痰瘀实邪的临床表现密切相关。
5.在ACE-I/D基因多态性研究中,脑梗死组ACE-DD基因型和D等位基因频率均明显高于正常对照组(P＜0.05)。ACE-DD基因型或D等位基因可能在脑梗死中起作用,且与脑梗死肝阳暴亢、风火上扰证密切相关,可能是该证候的遗传易感因素。脑梗死组患者DD基因型患者血浆AngⅡ水平显著增高,且肝阳暴亢,风火上扰证患者增高更显著。DD基因型导致血浆AngⅡ水平增高可能是中医肝阳暴亢,风火上扰证的遗传易感因素。
结论与缺血性脑卒中相关的基因多态性可以通过影响相关临床表型的表达间接影响中医中风的临床证候,即:表现相同证候的不同患者可能存在有某种程度的遗传相似性,而遗传基因的不同可能是某些证候的遗传易感因素。LDL的增高与HDL的降低,血粘度的改变,A-455等位基因与风痰瘀血,痹阻脉络证关系密切,不同LDL-R基因类型可能通过影响血脂代谢而使缺血性脑卒中患者表现不同的临床证候类型,A+等位基因是缺血性脑卒中患者表现风痰瘀血、痹阻脉络证候的遗传易感因素。DD基因型导致血浆AngⅡ水平增高可能是中医肝阳暴亢,风火上扰证的遗传易感因素。
Objectives: Cerebral arterial thrombosis was most common disease because of cerebral atherosclerosis or thromboembolism, its high disease incidence rate, the high mortality rate that had caused the paralysis, the aphasia and the aphrenia and caused patient's survival quality to be low. The significant disease had threatened to our country people health. Traditional Chinese medicine syndrome of diagnosis has much subjectivity, which affects constancy of diagnosing syndrome and repeatability of curative effect. Different pattern syndrome of cerebral arterial thrombosis maybe had different etiological factor and pathogenesis because of the distinct hereditary basis, cerebral arterial thrombosis had vary clinical feature.
Therefore, we planed to traditional Chinese medicine differentiation of symptoms and signs cerebral arterial thrombosis patients pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti-vein and pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind. We carried the relevant analysis of the gene polymorphism distribution and the clinical phenotype characteristic on the patient and healthy people's genes ofβ- fibrinogen - 455G/A, angiotensin-convertion enzyme (ACE), low density lipoprotein acceptor (LDL-R).To research the relations of traditional Chinese medicine syndrome and related gene distribution, clinical phenotype characteristic of cerebral arterial thrombosis of different Chinese medicine syndrome, revealed biology foundation and inherent axiom of cerebral arterial thrombosis of different Chinese medicine syndrome from the gene - disease - syndrome point of view, preliminary revealed modern medicine biology foundation of traditional Chinese medicine syndrome. Methods: According to research purpose, this experiment adopted the large sample, the parallel comparison, multi-central, the cross section research testing method. In nerve internal medicine department of Hubei Province hospital of traditional Chinese medicine, Wuhan first hospital, ZHONG NAN hospital of Wuhan university, collected cerebral infarction patients altogether were 410 examples, after screening , consistent with standard and complete effective data of the cases were 382 examples; collected healthy control group 200 examples.
Collected the clinical symptoms, the objective sign and the correlation data; Collected blood sample, extract whole blood DNA; adopted polymerase chain reaction restrictive fragment length polymorphism (PCR-RFLP) method to examine the gene polymorphism ofβ-fibrinogen - 455G/A, angiotensin-convertion enzyme (ACE), low density lipoprotein acceptor (LDL-R). We analyzed the relations of related gene distribution, disease clinical phenotype characteristic and traditional Chinese medicine syndrome of cerebral arterial thrombosis.
Results: 1. the common data 382 examples of cerebral infarction group: Masculine 206 examples, feminine 176 examples; The average age is 67.8±13.1, 40-49 year old of 46 examples, 50-59 year old of 89 examples, 60-69 year old of 137 examples, 70-79 year old of 110 examples; In the medical history the data has the hypertension patient 219 examples, the rheumatic heart patient 34 examples, the coronary artery disease 98 examples, the diabetes patient 113 examples, the hyperlipemia 206 examples, smoke 134 examples, drink wine 78 examples, has the cerebrovascular disease high-risk factor family history 261 examples.
pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein 237 examples, pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind 145 examples. Healthy control group: Masculine 107 examples, feminine 93 examples; The average age is 63.7±14.5, 40-49 year old of 24 examples, 50-59 year old of 58 examples, 60-69 year old of 87 examples, 70-79 year old of 31 examples; In the medical history haven't heart cerebrovascular diseases and so on hypertension, coronary artery disease, cerebral infarction, bodily various systems has no significant disease, smoke 51 examples, drink wine 37 examples, has the cerebrovascular disease high-risk factor family history 84 examples.
2. hyperactivity of liver-YANG, febrile disease complicated by wind syndrome of patient's contractive pressure and resting heart rate obviously to be higher than the hyperactivity of liver-YANG, febrile disease complicated by wind syndrome of patient in the acute stage of cerebral arterial thrombosis, which coincidence with pathogenesis of febrile disease complicated by wind, "RE XING YAN SHANG". The number of white blood corpuscle of blood Routine in patients are higher than the healthy control group, which hint to be inflammatory reaction in the body of cerebral arterial thrombosis acute stage, this result is similar with related research of "the near future infect is the stroke causative factor", which provide the mentality of traditional Chinese medicine disintoxicating, modern medicine anti-inflammatory, anti-infection to obviate stroke. The raised blood-fat is the independence hazard factor of cerebral infarction. The high of LDL and the low of HDL are the one of biochemical indicators to distinguish pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein and pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind. The blood viscosity's change is one of factors of cerebral infarction acute stage, the blood viscosity's change in cerebral infarction acute stage has close relations with pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein, which provides the theory basis for improving circulation by using drug for invigorating blood circulation and eliminating stasis.
3. In the gene polymorphism research,β- fibrinogen A- 455 allele concerned with cerebral infarction, this kind of dependablity is an independent risk factor opposite to other danger factors. A-455 allele is highly related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. A-455 allele has phlegm stasis pattern syndrome characteristic in clinical manifestation, possibly through affects the level of blood plasma fibrinogen, and adjusts hemorheology. Therefore, A-455 allele possibly is the genetic predisposition symbol of pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein in cerebral arterial thrombosis.
4. In LDL-R gene polymorphism research, We discovered that the anemogenous phlegm stagnant blood, arthralgia spasm anti- vein pattern syndrome patient's A+ allele frequency obviously is higher than the healthy control group and pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind. Indicate that A+ allele is closely related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein, A+ allele is genetic predisposition factor of stroke patient's pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein.
At the same time, high blood TG and LDL is closely related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti-vein, high blood TG and LDL patient show pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein in clinical, which agree without prior consultation with academic viewpoint of blood-fat belonging to Chinese medicine phlegm muddy. But the low level of blood HDL is closely related to pattern syndrome of hyperactivity of liver-YANG, febrile disease complicated by wind, hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome of the patient's blood HDL level is obviously lower than anemogenous phlegm stagnant blood, arthralgia spasm anti-vein pattern syndrome of patient and the healthy crowd.
Above results prompt, the different LDL-R gene type possibly through affects the blood lipid metabolism to cause the stroke patient to display the different clinical pattern syndrome, A+ allele is genetic predisposition factor of stroke patient's pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. But the different level of blood lipid also displays the different syndrome characteristic. The clinical manifestation of rising blood lipid is close related to the clinical manifestation of Chinese medicine phlegm stasis solid evil. 5. In the ACE-I/D gene polymorphism research, the ACE-DD genotype and the D allele of cerebral infarction group frequency obviously are higher than the normal control group (P<0.05). ACE-DD genotype or D allele possibly has an effect in cerebral infarction, and is close related to cerebral infarction of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome, which possibly is the genetic predisposition symbol. DD genotype patients of the cerebral infarction group obviously has high level of blood Ang II, patients of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome has more higher level of blood Ang II.The DD genotype lead to the higher level of blood Angll,which possibly is the diagnosis genetic predisposition symbol of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome of traditional Chinese medicine.
Conclusion: Gene polymorphism related to cerebral arterial thrombosis may indirectly influence Chinese medicine pattern syndrome clinical of stroke through influence on the expression of clinical phenotype, Appearance the same syndrome of the different patients possibly exist some degree of heredity similarity, the different genetic gene may be genetic predisposition factor of some syndrome. Raised LDL, lowered HDL, the change of blood viscosity and A—455 allele are close related to pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. The different LDL-R gene type cause the stroke patient to different clinical syndrome possibly through influence the blood lipid metabolism, A+ allele is genetic predisposition factor of stroke patient's pattern syndrome of anemogenous phlegm stagnant blood, arthralgia spasm anti- vein. The DD genotype lead to the higher level of blood Ang II, which possibly is the diagnosis genetic predisposition symbol of hyperactivity of liver-YANG, febrile disease complicated by wind pattern syndrome of traditional Chinese medicine.
引文
1.Tanizaki Y,Kiyohara Y Fujishima M.Incidence and risk factors for subtypes of cerebral infarction in a general population:the hisayama study.Stroke,2000,31(11):2616.
2.秦震.心脑血管的危险因素及预防对策.中国慢性病预防与控制.1995,3(5):193.
3.杜贻萌,王克志.缺血性脑卒中的分子遗传学研究进展.现代诊断与治疗.2002,13(4):122.
4.马丽媛,王文,刘力生.中国人群缺血性脑卒中相关基因的多态性分析.高血压杂志.2003,11(2):611.
5.镰田宽,等.脑卒中的易感基因.日本医学介绍.2004,25(1):2.
6.Xin Tu,Jinzhou Tian,Jinwen Tu,et al.Association between Intron 6 Polymorphisms in LPL Gene and Cerebral Infarction in Chinese Han Race Patients with Essential Hypertension.Stroke,2003.Jan
7.Jinwen Tu,Xin Tu,Jinming Wang,et al.A Study of Lipoprotein Lipase Gene Intron 8 Polymorphisms in Chinese Hart Race Essential Hypertension Patients.International Journal of Cardiology.2004(in print)
8.张道亮,涂欣.痰浊壅盛型原发性高血压患者脂蛋白脂酶基因内含子8多态性研究.中医药学报.2002,20(1):34.
[1]F1etcherRH,Clinicalepidemiology[M].Thirdedition.LondoWilliams &Wilkins.1996.75-93.
[2]闫永平.临床现况调查.见:李良寿主编.临床医学研究原理与方[M].第2版.西安:陕西科学技术出版社,2000.93-103.
[3]国家中医药管理局医政司脑病急症协作组.中风病诊断与疗效评定标准.北京中医药大学学报,1996.19(1):55-56.
[4]国家中医药管理局脑病急症科研组.中风病辨证诊断标准.北京中医药大学学报;1991,17(3):64-66.
[5]郑悦,桂冰.近期感染和缺血性脑中风的关系探讨.辽宁医学杂志,2003,17(4):102
[6]常富业,王永炎.中风病毒邪论[J].北京中医药大学学报,2004,27(1):3-6.
[7]李澎涛,王永炎.“毒损脑络”病机假说的形成及其理论与实践意义[J].北京中医药大学学报,2001,24(1):1-6.
[1]GrantPJ.Polymorphismsofcoagulation/fibrinolys isgenes:gene environ mentinter action sandcas cularrisk[J].Prostagland in sLeukot Essent Fatty Acids,2003,57(4-5):437.
[2]WilhelmsenL,Svardsuddk,Korsan Bengtsenk,etal.Fibri nogenasa riskfacf or forstrokeandmycardialinfarct ion[J].NEnglJMed,2004,11:501.
[3]ErnstEWK.Fibrinogenandcardiovascularrisk[J].VascMed,2002,10:115.
[4]GardemannA,SchwartzO,HaberboschW.Positiveassociationof thebeta fibrinogenHl/H Geneva riation tobasal fibrinogen level sandtothein cr easein fibrinogenconcentrat ionduringacutephasereact ionbutnot tocoronar yarterydiseaseandmyocardial infarc tion[J].ThrombHaemost,2004,77(6):110.
[5]HumphriesSE,CookM,Dubowi tzM,etal.DubowitsM.Roleofgenet icvaria tionat the fibrinogenlocus indeterminationofplas mafibrinogenconcentrati ons[J].Lancet,2003,1(54):145.
[6]董庆林,张晨.β-纤维蛋白原-455G/A基因多态性与脑梗死的相关性研究.临床神经病学杂志.2004,17:164-166.
[7]蒲传强,郎森阳,吴卫平,等.脑血管病学[M].北京:人民军医出版社,1999,1178-1791.
[8]LiaoD,MyerskR,HuntS,et al.Familial history of strok eand stroke risk[J].Stroke,2002,28:908.
[9]HumphriesSE.DNA poly morphism of theapolip oproteingenes the iruse in the investigation of the genetic component of hyperlipide miaanda the rosclerosis.Atherosclerosis,2002,72:89-95.
[10]俞民澍,邱信芳,薛京伦,主编.医学分子遗传学.北京:科学出版社,1990.327-330.
[11]GrantPJ.Polymorphismsofcoagulation/fibrinolysisgenes:geneLeuk otEssentFattyAcids,2003,57(4-5):437.
[12]WilhelmsenL,Svardsuddk,Korsan2Bengtsenk,etal.Fibrinogenasaris kfacforforstrokeandmycardialinfarction[J].NEnglJMed,2004,311:501.
[13]ErnstEWK.Fibrinogenandcardiovascularrisk[J].VascMed,2001,2:115.
[14]GardemannA,SchwartzO,HaberboschW.Positiveassociationofthebeta fibrinogenH1/H2genevariationtobasalfibrinogenlevelsandtotheincreasein fibrinogenconcentrationduringacutephasereactionbutnottocoronaryartery diseaseandmyocardialinfarc2tion[J].Thrombaaemost,2002,77(6):1120.
[15]HumphriesSE,CookM,DubowitzM,etal.DubowitsM.Roleofgeneticvaria tionatthefibrinogenlocusindeterminationofplas2mafibrinogenconcentrati ons[J].Lancet,2003,1(54):1452.
[16]NishiumaS,KarioK,YakushijinK.Geneticvariationinthepro2moterre gion of the B-fibrino gengeneisassociatedwithischemicstrokeinJapanese population[J].BloodCoagulationFibrinoly2sis,2002,9:373.
[1]郭津津,郭阳,王富伟,等.低密度脂蛋白受体基因多态性与血脂含量的关系[J].中国医科大学学报,2005,27(4):407-412.
[2]郑芳,周新,崔天盆.汉族人低密度脂蛋白受体基因多态性对血脂,脂蛋白和载脂蛋白水平的影响[J].中华医学遗传学杂志,2004,17(2):138-139.
[3]刘爱萍,詹思延,李立明.低密度脂蛋白受体基因多态性与高脂血症的关系[J].中华流行病学杂志,2005,22(4):30 33.
[4]KorenE.Trighjceride,enrichedlipoproteinparticalescorrelateswit htheseverityofcoronaryar terydisease[J].Atherosclerosis,2002,122:1051.
[5]YamamotoT,DavisCG,Brown:MS,etal.ThehumanLDLre2cepter:acrystein e-richproteinwithmultiplehluSequencesinitsmRNhlJ2,cell,2003,39(1):27
[6]YamamotoT,BishopRW,BrownMS,GoldsteinJL,RusselDW.Deletionincyst eine-richregionofLDLreceptorimpedestransporttocellsurfaceinWHHLrabbit .science2002,232:1230
[7]BrownMS,GoldstinJL.Areceptor-mediatdepathwayforcholes2terolhom eostasis.Science2004,232:34
[8]GodsteinJL,KitaT,BrownMS.defectivelipoproteinreceptorandathero sclerosis:lesionfromananimalcounterpartoffamiliarthper2cholesterolemi a.NEnglJMed,2003,309:288
[9]GoldsteinJL,BrownMS.Familialhypercholesterolemia.ThemetabolicB asisoflnheritedDisease,6thedn.NewYork:McGraw-Hill.2003,1215
[1]张旭,夏君慧,金得辛,林捷,叶好好.血管紧张素转化酶基因多性与脑梗死危险因素的关系.中华流行病学杂志,2001,12:4352438
[2]王新德.各类脑血管疾病诊断要点.中华神经科杂志,1996,29:37381
[3]Guidelinessubcommittee.1999worldhealthorganization2internat ionalsocietyhypertensionguidelinesforthemanagementofhypertension.JHy pertens,2003,7:151-183
[4]TiretL,RigatB,VisvikisS,BredaC,CorvolP,CambienF,etal.Evdenc e,fromcombinedsegregationandlinkageanalysis,thatavariantoftheagiotens inI2convertingenzyme(ACE)genecontrolsplasmaACElevels.AmHumGenet,2002,51:197-205
[5]MarkusH,BarleyJ,LuntR,BlandM,JefferyS,CarterNickD,etal.hgio tensin2convertingenzymegenedeletionpolymorphism:anewriskfactorforlcun arstrokebutnotcarotidatheroma.Stroke,2005,26:329-333
[6]PullicinoP,KwenP,GreenbergS,BeckerAL,GlenisterN.Angiotensin covertingenzymegeneandlacunarstroke.Stroke,2003,27:568-570
[7]许贻白,王贤军,诸金水,王亚仙,戴利成,等.血管紧张素转化酶因多态性与急性脑血管病的关系.中华神经科杂志,2005,6:152-155
[8]谈红,张国元,尤乃祯,黄超,刘建平.冠心病患者血管紧张素转酶基因多态性及其与血管紧张素转化酶水平的关系.中国动脉硬化志,2006,6:134-136
[9]DoiY,YoshinariM,YoshizumiH,IbayashiS,WakisakaM,FujishimaM.Pol ymorphismoftheangiotensin2convertingenzyme(ACE)geneinpatientswthrombo ticbraininfarction.Atherosclerosis,2004,132:145-150
[1O]张玉平,李建军,刘颖,王晶.氯沙坦对球囊成形术后兔血管内膜生和基质金属蛋白酶2及其抑制剂表达的影响.中国动脉硬化杂志2003,11:36-40
[1]BrassBM,ShakerLA.Familyhistoryinpatientswithtransientischemicattacks[J].Stroke,2001,22:837-841.
[2]KielyDK,WilfPA,CupplesLA,etal.Familialaggregationofstroke[J].Stroke,2003,24:1366-1371.
[3]JousilahtiP,RastenyteD,TuomilehtoJ,etal.Parentalhistoryofcardio2vasculardis easeandriskofstroke.Aprospectivefollow2upof14371 middle2agedmenandwomeninFin land[J].Stroke,2004,28:1361-1366.
[4]GraffagninoC,GseckiA,DoigG,etal.Theimportanceoffamilyhistoryincerebrov asculardisease[J].Stroke,2004,25:1599-1604.
[5]BrassLM,IsaacsohnJL,MerikangasKR,etal.Astudyoftwinsandstroke[J].Stroke ,2002,23:221-223.
[6]MaedaY,IkedaU,EbataH,etal.Angiotension2convertingenzymegenepolymorp hisminhypertensiveindividualswithparentalhistoryofstroke[J].Stroke,2004,27:1521-1523.
[7]KarioK,KanaiN,SaitoK,etal.Ischemicstrokeandthegeneforan2giotensin2conv ertingenzymeinJapanesehypertensives[J].Circulation,2003,93:1630.
[8]TakamiS,ImaiY,KatsuyaT,etal.Genepolymorphismofthereninan2giotensinsys temassociateswithriskforlacunarinfarction.TheOhasamastudy[J].AmJHypertens,2000,13:121-127.
[9]管立学,张爱娟,宋保华,等.血管紧张素原基因CD235MetyThr变异与脑梗塞发病的关系[J].中华医学遗传学杂志,2004,17(5):336-339.
[10]KesslerC,SpitzerC,StauskeD,etal.TheapolipoproteinEandbeta2fibrinogenG/A2455genepolymorphismsareassociatedwithischemicstrokeinvolvinglarge2vesseldise ase[J].ArteriosclerThrombVascBi2ol,2006,17(11):2880-2884.
[11]NishiumaS,KarioK,YakushijinK,etal.Geneticvariationinthepro2moterregion ofthebeta2fibrinogengeneisassociatedwithischemicstrokeinaJapanesepopulation[J].Blo odCoagulFibrinolysis,2004,9(4):373-379.
[12]PoortSR,RosendaalFR,ReitsmaPH,etal.Acommongeneticvaria2tioninthe3.2untranslatedregionoftheprothrombingeneisassociatedwithelevatedplasmaprothrombinl evelsandanincreaseinvenousthrombosis[J].Blood,2004,15:88(10):3698-3703.
[13]De2StefanoV,ChiusoloP,PaciaroniK,etal.ProthrombinG20210Amutantgenot ypeisafiskfactorforcerebrovascularischemicdiseaseinyoungpatients[J].Blood,2005,15:91(10):3562-3565.
[14]GreenF,KelleherC,WilkesH,etal.Acommongeneticpolymorphismassociated withlowercoagulationfactorⅧevelsinhealthyindividuals[J].Arterioscler2Thromb,2001,11(3):540-546.
[15]SahaN,LiuY,HengCK,etal.Associationoffactorgenotypewithplasmafactoract ivityandantigenlevelsinhealthylndianadultsandinteractionwithtriglycerides[J].Arterios clerThromb,2004,14(12):1923-1927.
[16]HeywoodDM,CarterAM,CattoAJ,etal.Polymorphismsofthefactorgeneandcir culatingF:Clevelsinrelationtacutecerebrovasculardiseaseandpoststrokemortality[J].St roke,2004,28(4):816-821.
[17]刘树杰,杨露春,王晓东,等.急性脑梗死患者血浆纤溶酶原激活物抑制剂活性及其启动子区域基因多态性研究[J].中华神经科杂志,2006,31(5):264-266.
[18]CattoAJ,CarterAM,SticklandM,etal.Plasminogenactivatorin2hibitor21(PAl 21)4G/5Gpromoterpolymorphismandlevelsinsubjectswithcerebrovasculardisease[J].T hrombHaemost,2004,77(4):730-734.
[19]SonodaA,MurataM,ItoD,etal.Associationbetweenplateletglyco2proteinIbalp hagenotypeandischemiccerebrovasculardisease[J].Stroke,2000,31(2):493-497.
[20]Gonzalez2ConejeroR,LozanoML,RiveraJ,etal.Polymorphismsofplateletme mbraneglycoproteinlbWassociatedwitharterialthromboticdisease[J].Blood,2002,15:92(8):2771-2776.
[21]CarterAM,CattoAJ,BamfordJM,etal.PlateletGPaPIAandGPIbvariablenumb ertandemrepeatpolymorphismsandmarkersofplateletactivationinacutestroke[J].Arterio sclerThrombVascBiol,2003,18(7):1124-1131.
[22]CarlssonLE,SantosoS,SpitzerC,etal.Thealpha2genecodingse2quenceT807/A873 oftheplateletcollagenreceptorintegrinalpha2be2ta1mightbeageneticriskfactorfort hedevelopmentofstrokeinyoungerpatients[J].Blood,2004,93(11):3583-3586.
[23]MoritaH,KuriharaH,TsubakiS,etal.Methylenetetrahydrofolatere2ductasegen epolymorphismandischemicstrokeinJapanese[J].Arte2riosclerThrombVascBiol,2002,18(9):1465-1469.
[24]KazuyaS,HiroakiN,TakaoS,etal.Roleofinsulinresistanceassociat2edwithcom pensatoryhyperinsulinemiainischemicstroke[J].Stroke,2001,27(1):37-43.
[25]NakataY,KatsuyaT,RakugiH,etal.Polymorphismofangiotensinconvertingenz yme,angiotensinogen,andapolipoproteinEgenesinaJapanesepopulationwithcerebrovasc ulardisease[J].AmJHypertens,2002,10(12Pt1):1391-1395.
[26]毕胜,潘尚哈,王德生,等.动脉粥样硬化性脑梗塞患者ACE基因与ATlR 基因多态性分析[J].中风与神经疾病杂志,2002,15(3):139-141.
[27]Aalto2 SetalaK,PalomakiH,MiettinenH,etal.Geneticriskfactorsandischaemic cerebrovasculardisease:roleofcommonvariationofthegenesencodingapolipoproteinsand angiotensin2convertingenzyme[J].ArmMed,2004,30(2):224-233.
[28]HuangP,KostulasK,HuangWX,etal.Lipoproteinlipasegenepoly2morphi smsinischaemicstrokeandcarotidstenosis.EurJClinlnvest,2000,27(9):740-742.
[1]徐会吾,杜晓泉.CT在缺血性中风辨证中的作用[J].陕西中医学院学报,2001,24(6):54
[2]周庆芳,刘华,许存森.出血性中风中医证型与颅脑核磁共振检查关系的研究[J].浙江中医杂志,2005,30(12):550
[3]魏丹,张东友,王金娥.脑出血中医临床证型与头颅CT表现的相关性[J].中医药研究,2001,15(3):26、43
[4]朱力莹,王求彬,何民.急性中风CT诊断结果与中医辨证分型的关系分析[J].中国中医药科技,2003,3(1):45
[5]余朝骏,侯键,吴永康,等.中风急性期中医辨证与头颅CT征象相关性的研究[J].成都中医药大学学报,2000,23(3):7-12
[6]张东友,王进.中风病中医临床证型的CT研究[J].湖北中医杂志,2003,20(2):21-23
[7]王顺道,任占利.中风病始发态证候与脑病理改变相关关系的研究[J].中国中医急症,2004,8(1):36-39
[8]梁伟雄,黄培新.中风病中医证候特征与脑病理改变的相关关系研究[J].新中医,2004,31(7):41-42
[9]刘岑.中风病的颅脑血流动力学研究附:75例中风病人TCD分析[J].中国中医药信息杂志,2003,3(2):18
[10]杨玉洁,张洁.脑梗塞患者TCD特征与中医辨证关系探讨[J].吉林中医药,2005,17(6):13
[11]王礼文,顾洪璋,葛亚东.血液流变学及血脂相关指标在中风诊断中的应用[J].中国微循环,2002,6(6):359
[12]王少华,张晶瑜,王利群.急性缺血性中风辨证与头颅CT相关指标的研究[J].辽宁中医杂志,2003,28(3):132
[13]黄炎明.中风患者的血脂变化及其与中医辨证关系的研究[J].中国医药学报,2005,11(003):10-11
[14]Xin Tu,Jinwen Tu,Xiuying Wen,et al.A Study of Lipoprotein Lipase GeneIntron 8 Polymorphisms in Chinese Han Race Essential Hypertension Patients.International Journal of Cardiology.2005.3
[15]张道亮,涂欣等.痰浊壅盛型原发性高血压患者脂蛋白脂酶基因内含子8多态性研究.中医药学报,2002.3:334-337.
[16]Russ AP,Maerz W,Ruzicka V,et al.Rapid detection of the hypertension-associated Met235-Thr allele of the human angiotensinogen gene.Human Mol Gen,1993,2:609-610.
[17].TakamiS,Imai Y,KatsuyaT,etal.Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction.The Ohasama study.Am J Hypertens.2000,13(2):1221-127
2.秦震.心脑血管的危险因素及预防对策.中国慢性病预防与控制.1995,3(5):193.
3.杜贻萌,王克志.缺血性脑卒中的分子遗传学研究进展.现代诊断与治疗.2002,13(4):122.
4.马丽媛,王文,刘力生.中国人群缺血性脑卒中相关基因的多态性分析.高血压杂志.2003,11(2):611.
5.镰田宽,等.脑卒中的易感基因.日本医学介绍.2004,25(1):2.
6.Xin Tu,Jinzhou Tian,Jinwen Tu,et al.Association between Intron 6 Polymorphisms in LPL Gene and Cerebral Infarction in Chinese Han Race Patients with Essential Hypertension.Stroke,2003.Jan
7.Jinwen Tu,Xin Tu,Jinming Wang,et al.A Study of Lipoprotein Lipase Gene Intron 8 Polymorphisms in Chinese Hart Race Essential Hypertension Patients.International Journal of Cardiology.2004(in print)
8.张道亮,涂欣.痰浊壅盛型原发性高血压患者脂蛋白脂酶基因内含子8多态性研究.中医药学报.2002,20(1):34.
[1]F1etcherRH,Clinicalepidemiology[M].Thirdedition.LondoWilliams &Wilkins.1996.75-93.
[2]闫永平.临床现况调查.见:李良寿主编.临床医学研究原理与方[M].第2版.西安:陕西科学技术出版社,2000.93-103.
[3]国家中医药管理局医政司脑病急症协作组.中风病诊断与疗效评定标准.北京中医药大学学报,1996.19(1):55-56.
[4]国家中医药管理局脑病急症科研组.中风病辨证诊断标准.北京中医药大学学报;1991,17(3):64-66.
[5]郑悦,桂冰.近期感染和缺血性脑中风的关系探讨.辽宁医学杂志,2003,17(4):102
[6]常富业,王永炎.中风病毒邪论[J].北京中医药大学学报,2004,27(1):3-6.
[7]李澎涛,王永炎.“毒损脑络”病机假说的形成及其理论与实践意义[J].北京中医药大学学报,2001,24(1):1-6.
[1]GrantPJ.Polymorphismsofcoagulation/fibrinolys isgenes:gene environ mentinter action sandcas cularrisk[J].Prostagland in sLeukot Essent Fatty Acids,2003,57(4-5):437.
[2]WilhelmsenL,Svardsuddk,Korsan Bengtsenk,etal.Fibri nogenasa riskfacf or forstrokeandmycardialinfarct ion[J].NEnglJMed,2004,11:501.
[3]ErnstEWK.Fibrinogenandcardiovascularrisk[J].VascMed,2002,10:115.
[4]GardemannA,SchwartzO,HaberboschW.Positiveassociationof thebeta fibrinogenHl/H Geneva riation tobasal fibrinogen level sandtothein cr easein fibrinogenconcentrat ionduringacutephasereact ionbutnot tocoronar yarterydiseaseandmyocardial infarc tion[J].ThrombHaemost,2004,77(6):110.
[5]HumphriesSE,CookM,Dubowi tzM,etal.DubowitsM.Roleofgenet icvaria tionat the fibrinogenlocus indeterminationofplas mafibrinogenconcentrati ons[J].Lancet,2003,1(54):145.
[6]董庆林,张晨.β-纤维蛋白原-455G/A基因多态性与脑梗死的相关性研究.临床神经病学杂志.2004,17:164-166.
[7]蒲传强,郎森阳,吴卫平,等.脑血管病学[M].北京:人民军医出版社,1999,1178-1791.
[8]LiaoD,MyerskR,HuntS,et al.Familial history of strok eand stroke risk[J].Stroke,2002,28:908.
[9]HumphriesSE.DNA poly morphism of theapolip oproteingenes the iruse in the investigation of the genetic component of hyperlipide miaanda the rosclerosis.Atherosclerosis,2002,72:89-95.
[10]俞民澍,邱信芳,薛京伦,主编.医学分子遗传学.北京:科学出版社,1990.327-330.
[11]GrantPJ.Polymorphismsofcoagulation/fibrinolysisgenes:geneLeuk otEssentFattyAcids,2003,57(4-5):437.
[12]WilhelmsenL,Svardsuddk,Korsan2Bengtsenk,etal.Fibrinogenasaris kfacforforstrokeandmycardialinfarction[J].NEnglJMed,2004,311:501.
[13]ErnstEWK.Fibrinogenandcardiovascularrisk[J].VascMed,2001,2:115.
[14]GardemannA,SchwartzO,HaberboschW.Positiveassociationofthebeta fibrinogenH1/H2genevariationtobasalfibrinogenlevelsandtotheincreasein fibrinogenconcentrationduringacutephasereactionbutnottocoronaryartery diseaseandmyocardialinfarc2tion[J].Thrombaaemost,2002,77(6):1120.
[15]HumphriesSE,CookM,DubowitzM,etal.DubowitsM.Roleofgeneticvaria tionatthefibrinogenlocusindeterminationofplas2mafibrinogenconcentrati ons[J].Lancet,2003,1(54):1452.
[16]NishiumaS,KarioK,YakushijinK.Geneticvariationinthepro2moterre gion of the B-fibrino gengeneisassociatedwithischemicstrokeinJapanese population[J].BloodCoagulationFibrinoly2sis,2002,9:373.
[1]郭津津,郭阳,王富伟,等.低密度脂蛋白受体基因多态性与血脂含量的关系[J].中国医科大学学报,2005,27(4):407-412.
[2]郑芳,周新,崔天盆.汉族人低密度脂蛋白受体基因多态性对血脂,脂蛋白和载脂蛋白水平的影响[J].中华医学遗传学杂志,2004,17(2):138-139.
[3]刘爱萍,詹思延,李立明.低密度脂蛋白受体基因多态性与高脂血症的关系[J].中华流行病学杂志,2005,22(4):30 33.
[4]KorenE.Trighjceride,enrichedlipoproteinparticalescorrelateswit htheseverityofcoronaryar terydisease[J].Atherosclerosis,2002,122:1051.
[5]YamamotoT,DavisCG,Brown:MS,etal.ThehumanLDLre2cepter:acrystein e-richproteinwithmultiplehluSequencesinitsmRNhlJ2,cell,2003,39(1):27
[6]YamamotoT,BishopRW,BrownMS,GoldsteinJL,RusselDW.Deletionincyst eine-richregionofLDLreceptorimpedestransporttocellsurfaceinWHHLrabbit .science2002,232:1230
[7]BrownMS,GoldstinJL.Areceptor-mediatdepathwayforcholes2terolhom eostasis.Science2004,232:34
[8]GodsteinJL,KitaT,BrownMS.defectivelipoproteinreceptorandathero sclerosis:lesionfromananimalcounterpartoffamiliarthper2cholesterolemi a.NEnglJMed,2003,309:288
[9]GoldsteinJL,BrownMS.Familialhypercholesterolemia.ThemetabolicB asisoflnheritedDisease,6thedn.NewYork:McGraw-Hill.2003,1215
[1]张旭,夏君慧,金得辛,林捷,叶好好.血管紧张素转化酶基因多性与脑梗死危险因素的关系.中华流行病学杂志,2001,12:4352438
[2]王新德.各类脑血管疾病诊断要点.中华神经科杂志,1996,29:37381
[3]Guidelinessubcommittee.1999worldhealthorganization2internat ionalsocietyhypertensionguidelinesforthemanagementofhypertension.JHy pertens,2003,7:151-183
[4]TiretL,RigatB,VisvikisS,BredaC,CorvolP,CambienF,etal.Evdenc e,fromcombinedsegregationandlinkageanalysis,thatavariantoftheagiotens inI2convertingenzyme(ACE)genecontrolsplasmaACElevels.AmHumGenet,2002,51:197-205
[5]MarkusH,BarleyJ,LuntR,BlandM,JefferyS,CarterNickD,etal.hgio tensin2convertingenzymegenedeletionpolymorphism:anewriskfactorforlcun arstrokebutnotcarotidatheroma.Stroke,2005,26:329-333
[6]PullicinoP,KwenP,GreenbergS,BeckerAL,GlenisterN.Angiotensin covertingenzymegeneandlacunarstroke.Stroke,2003,27:568-570
[7]许贻白,王贤军,诸金水,王亚仙,戴利成,等.血管紧张素转化酶因多态性与急性脑血管病的关系.中华神经科杂志,2005,6:152-155
[8]谈红,张国元,尤乃祯,黄超,刘建平.冠心病患者血管紧张素转酶基因多态性及其与血管紧张素转化酶水平的关系.中国动脉硬化志,2006,6:134-136
[9]DoiY,YoshinariM,YoshizumiH,IbayashiS,WakisakaM,FujishimaM.Pol ymorphismoftheangiotensin2convertingenzyme(ACE)geneinpatientswthrombo ticbraininfarction.Atherosclerosis,2004,132:145-150
[1O]张玉平,李建军,刘颖,王晶.氯沙坦对球囊成形术后兔血管内膜生和基质金属蛋白酶2及其抑制剂表达的影响.中国动脉硬化杂志2003,11:36-40
[1]BrassBM,ShakerLA.Familyhistoryinpatientswithtransientischemicattacks[J].Stroke,2001,22:837-841.
[2]KielyDK,WilfPA,CupplesLA,etal.Familialaggregationofstroke[J].Stroke,2003,24:1366-1371.
[3]JousilahtiP,RastenyteD,TuomilehtoJ,etal.Parentalhistoryofcardio2vasculardis easeandriskofstroke.Aprospectivefollow2upof14371 middle2agedmenandwomeninFin land[J].Stroke,2004,28:1361-1366.
[4]GraffagninoC,GseckiA,DoigG,etal.Theimportanceoffamilyhistoryincerebrov asculardisease[J].Stroke,2004,25:1599-1604.
[5]BrassLM,IsaacsohnJL,MerikangasKR,etal.Astudyoftwinsandstroke[J].Stroke ,2002,23:221-223.
[6]MaedaY,IkedaU,EbataH,etal.Angiotension2convertingenzymegenepolymorp hisminhypertensiveindividualswithparentalhistoryofstroke[J].Stroke,2004,27:1521-1523.
[7]KarioK,KanaiN,SaitoK,etal.Ischemicstrokeandthegeneforan2giotensin2conv ertingenzymeinJapanesehypertensives[J].Circulation,2003,93:1630.
[8]TakamiS,ImaiY,KatsuyaT,etal.Genepolymorphismofthereninan2giotensinsys temassociateswithriskforlacunarinfarction.TheOhasamastudy[J].AmJHypertens,2000,13:121-127.
[9]管立学,张爱娟,宋保华,等.血管紧张素原基因CD235MetyThr变异与脑梗塞发病的关系[J].中华医学遗传学杂志,2004,17(5):336-339.
[10]KesslerC,SpitzerC,StauskeD,etal.TheapolipoproteinEandbeta2fibrinogenG/A2455genepolymorphismsareassociatedwithischemicstrokeinvolvinglarge2vesseldise ase[J].ArteriosclerThrombVascBi2ol,2006,17(11):2880-2884.
[11]NishiumaS,KarioK,YakushijinK,etal.Geneticvariationinthepro2moterregion ofthebeta2fibrinogengeneisassociatedwithischemicstrokeinaJapanesepopulation[J].Blo odCoagulFibrinolysis,2004,9(4):373-379.
[12]PoortSR,RosendaalFR,ReitsmaPH,etal.Acommongeneticvaria2tioninthe3.2untranslatedregionoftheprothrombingeneisassociatedwithelevatedplasmaprothrombinl evelsandanincreaseinvenousthrombosis[J].Blood,2004,15:88(10):3698-3703.
[13]De2StefanoV,ChiusoloP,PaciaroniK,etal.ProthrombinG20210Amutantgenot ypeisafiskfactorforcerebrovascularischemicdiseaseinyoungpatients[J].Blood,2005,15:91(10):3562-3565.
[14]GreenF,KelleherC,WilkesH,etal.Acommongeneticpolymorphismassociated withlowercoagulationfactorⅧevelsinhealthyindividuals[J].Arterioscler2Thromb,2001,11(3):540-546.
[15]SahaN,LiuY,HengCK,etal.Associationoffactorgenotypewithplasmafactoract ivityandantigenlevelsinhealthylndianadultsandinteractionwithtriglycerides[J].Arterios clerThromb,2004,14(12):1923-1927.
[16]HeywoodDM,CarterAM,CattoAJ,etal.Polymorphismsofthefactorgeneandcir culatingF:Clevelsinrelationtacutecerebrovasculardiseaseandpoststrokemortality[J].St roke,2004,28(4):816-821.
[17]刘树杰,杨露春,王晓东,等.急性脑梗死患者血浆纤溶酶原激活物抑制剂活性及其启动子区域基因多态性研究[J].中华神经科杂志,2006,31(5):264-266.
[18]CattoAJ,CarterAM,SticklandM,etal.Plasminogenactivatorin2hibitor21(PAl 21)4G/5Gpromoterpolymorphismandlevelsinsubjectswithcerebrovasculardisease[J].T hrombHaemost,2004,77(4):730-734.
[19]SonodaA,MurataM,ItoD,etal.Associationbetweenplateletglyco2proteinIbalp hagenotypeandischemiccerebrovasculardisease[J].Stroke,2000,31(2):493-497.
[20]Gonzalez2ConejeroR,LozanoML,RiveraJ,etal.Polymorphismsofplateletme mbraneglycoproteinlbWassociatedwitharterialthromboticdisease[J].Blood,2002,15:92(8):2771-2776.
[21]CarterAM,CattoAJ,BamfordJM,etal.PlateletGPaPIAandGPIbvariablenumb ertandemrepeatpolymorphismsandmarkersofplateletactivationinacutestroke[J].Arterio sclerThrombVascBiol,2003,18(7):1124-1131.
[22]CarlssonLE,SantosoS,SpitzerC,etal.Thealpha2genecodingse2quenceT807/A873 oftheplateletcollagenreceptorintegrinalpha2be2ta1mightbeageneticriskfactorfort hedevelopmentofstrokeinyoungerpatients[J].Blood,2004,93(11):3583-3586.
[23]MoritaH,KuriharaH,TsubakiS,etal.Methylenetetrahydrofolatere2ductasegen epolymorphismandischemicstrokeinJapanese[J].Arte2riosclerThrombVascBiol,2002,18(9):1465-1469.
[24]KazuyaS,HiroakiN,TakaoS,etal.Roleofinsulinresistanceassociat2edwithcom pensatoryhyperinsulinemiainischemicstroke[J].Stroke,2001,27(1):37-43.
[25]NakataY,KatsuyaT,RakugiH,etal.Polymorphismofangiotensinconvertingenz yme,angiotensinogen,andapolipoproteinEgenesinaJapanesepopulationwithcerebrovasc ulardisease[J].AmJHypertens,2002,10(12Pt1):1391-1395.
[26]毕胜,潘尚哈,王德生,等.动脉粥样硬化性脑梗塞患者ACE基因与ATlR 基因多态性分析[J].中风与神经疾病杂志,2002,15(3):139-141.
[27]Aalto2 SetalaK,PalomakiH,MiettinenH,etal.Geneticriskfactorsandischaemic cerebrovasculardisease:roleofcommonvariationofthegenesencodingapolipoproteinsand angiotensin2convertingenzyme[J].ArmMed,2004,30(2):224-233.
[28]HuangP,KostulasK,HuangWX,etal.Lipoproteinlipasegenepoly2morphi smsinischaemicstrokeandcarotidstenosis.EurJClinlnvest,2000,27(9):740-742.
[1]徐会吾,杜晓泉.CT在缺血性中风辨证中的作用[J].陕西中医学院学报,2001,24(6):54
[2]周庆芳,刘华,许存森.出血性中风中医证型与颅脑核磁共振检查关系的研究[J].浙江中医杂志,2005,30(12):550
[3]魏丹,张东友,王金娥.脑出血中医临床证型与头颅CT表现的相关性[J].中医药研究,2001,15(3):26、43
[4]朱力莹,王求彬,何民.急性中风CT诊断结果与中医辨证分型的关系分析[J].中国中医药科技,2003,3(1):45
[5]余朝骏,侯键,吴永康,等.中风急性期中医辨证与头颅CT征象相关性的研究[J].成都中医药大学学报,2000,23(3):7-12
[6]张东友,王进.中风病中医临床证型的CT研究[J].湖北中医杂志,2003,20(2):21-23
[7]王顺道,任占利.中风病始发态证候与脑病理改变相关关系的研究[J].中国中医急症,2004,8(1):36-39
[8]梁伟雄,黄培新.中风病中医证候特征与脑病理改变的相关关系研究[J].新中医,2004,31(7):41-42
[9]刘岑.中风病的颅脑血流动力学研究附:75例中风病人TCD分析[J].中国中医药信息杂志,2003,3(2):18
[10]杨玉洁,张洁.脑梗塞患者TCD特征与中医辨证关系探讨[J].吉林中医药,2005,17(6):13
[11]王礼文,顾洪璋,葛亚东.血液流变学及血脂相关指标在中风诊断中的应用[J].中国微循环,2002,6(6):359
[12]王少华,张晶瑜,王利群.急性缺血性中风辨证与头颅CT相关指标的研究[J].辽宁中医杂志,2003,28(3):132
[13]黄炎明.中风患者的血脂变化及其与中医辨证关系的研究[J].中国医药学报,2005,11(003):10-11
[14]Xin Tu,Jinwen Tu,Xiuying Wen,et al.A Study of Lipoprotein Lipase GeneIntron 8 Polymorphisms in Chinese Han Race Essential Hypertension Patients.International Journal of Cardiology.2005.3
[15]张道亮,涂欣等.痰浊壅盛型原发性高血压患者脂蛋白脂酶基因内含子8多态性研究.中医药学报,2002.3:334-337.
[16]Russ AP,Maerz W,Ruzicka V,et al.Rapid detection of the hypertension-associated Met235-Thr allele of the human angiotensinogen gene.Human Mol Gen,1993,2:609-610.
[17].TakamiS,Imai Y,KatsuyaT,etal.Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction.The Ohasama study.Am J Hypertens.2000,13(2):1221-127