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中医综合方案治疗糖尿病基础急性缺血中风疗效观察及作用机制探讨
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摘要
背景
     中风病被称为“人类健康的头号杀手”,具有高患病率、高病死率、高致残率和高复发率的特点,是一种严重危害人类健康的全球性问题。脑血管病是我国人口死亡的第二位原因,其中1/3的患者死亡,另1/3的患者终身残疾,给社会和家庭都增加了不少的负担。
     治疗和防治中风病,首要的问题是对中风病发病危险因素的研究,通过控制这些危险因素来防治中风病。糖尿病是中风病的重要危险因素之一,也是动脉粥样硬化性脑血管疾病的独立危险因素之一。因此从治疗危险因素的角度对中风病进行治疗,并探讨其可能的作用机理,是降低致残率和死亡率,提高患者生活质量和防止复发的重要途径之一。中医药在治疗中风病方面有独到的优势,面对多因素所致的中风危急重症病人,临床上采取以辨证论治为核心的综合治疗方案,发挥综合效能,才能取得最好的疗效。本课题所用中医综合治疗方案包括中风协定方(益脑康胶囊),华佗再造丸和灯盏细辛注射液。
     目的
     本研究旨在采用多种统计方法,对“十五”数据库进行回顾性分析,探讨中医综合治疗方案对急性缺血中风合并糖尿病阴类证患者在神经功能缺损程度、残障程度、日常生活能力、中医症征积分等方面的治疗作用;并通过动物实验,来探讨益脑康胶囊治疗急性缺血中风的疗效,从胰岛素抵抗角度来探讨益脑康胶囊治疗急性缺血中风的可能作用机制。
     方法
     本研究临床部分依托国家“十五”攻关项目“急性缺血中风辨证规范和疗效评价的示范研究”数据库,利用SPSS 13.0统计分析软件进行回顾性分析。观察在中医综合方案治疗组中,合并糖尿病和不合并糖尿病的急性缺血中风患者其中医症征积分、神经功能缺损水平、残障水平、生活自理能力等方面的改善情况;观察有糖尿病病史的急性缺血中风患者在经中医综合治疗方案或西医基础治疗后,其中医症征积分、神经功能缺损水平、残障水平、生活自理能力等的改善情况,来探讨中医综合治疗方案对急性缺血中风合并糖尿病阴类证患者的治疗效果。
     本研究实验部分将115只大鼠随机分为正常组、动脉粥样硬化组、复合模型组、益脑康预防组、益脑康治疗组、立普妥治疗组。采用高脂膳食喂养法复制动脉粥样硬化大鼠模型,在此基础上复制缺血再灌注大鼠模型,从行为学、生化指标、病理等方面对模型进行评价;干预上分别给予预先灌服益脑康胶囊(预用益脑康组)和正常治疗时点的益脑康胶囊、立普妥胶囊。本文分别从行为学(ZeaLonga评分法评价神经行为学的改变)、生化指标(血糖、胰岛素、脂联素、游离脂肪酸,并计算胰岛素抵抗指数)、免疫组化(颈动脉脂联素表达水平的异常)、脑组织病理、大鼠脑含水量等方面来评价益脑康胶囊的治疗作用。观察益脑康胶囊对上述各项指标的作用。从胰岛素抵抗角度来探讨益脑康胶囊治疗急性缺血中风大鼠的可能作用机制。
     结果
     临床部分:中医综合治疗组中合并糖尿病和不合并糖尿病的急性缺血中风患者经治疗后,两组患者在神经功能缺损程度、残障水平、日常生活能力、中医症征积分(严重程度、对生活的影响)方面差异均无统计学意义(P>0.05)。
     合并糖尿病的急性缺血中风患者分别经中医综合治疗方案和西医基础治疗后,结果:神经功能缺损程度,与基线NIHSS总分相比较,两组在第21天的评分降幅有显著性差异,具有统计学意义(P<0.05);残障水平,两组21天GOS比较差异有统计学意义(P<0.05);日常生活能力,在第21天,随访的60天和90天,BI指数均无显著性差异(P>0.05);中医症征积分中对生活的影响方面,在21天、90天比较差异有统计学意义(P<0.05)。
     由以上可以看出中医综合治疗方案可以改善患者神经功能缺损;减轻21天的残障水平;可以减轻治疗后21天和90天的中医症征;提高患者90天随访的生活能力;随着随访时间的延长,中医综合治疗方案有提高患者生存质量的趋势。可见此中医综合治疗方案治疗急性缺血血中风合并糖尿病阴类证患者确有疗效,值得进一步探讨。
     实验部分:本研究采用高脂饲料喂养诱发高血脂、胰岛素抵抗大鼠,在此基础上复制急性缺血再灌注大鼠模型,灌服益脑康胶囊治疗7天后,治疗前后对比,益脑康胶囊可降低模型鼠的血糖、胰岛素、胰岛素抵抗指数,立普妥可降低模型鼠的胰岛素水平,二者对脂联素水平影响不大,立普妥可降低模型鼠游离脂肪酸水平,预用益脑康胶囊可有效降低模型鼠游离脂肪酸水平。治疗后三个干预组组间比较,益脑康降血糖效果优于立普妥,三组在降低胰岛素水平、胰岛素抵抗指数、脂联素方面差异无显著性,在降低游离脂肪酸方面,预用益脑康组优于益脑康组,与立普妥组比较差异无显著性。
     模型鼠颈动脉脂联素免疫组化显示,治疗前复合模型组血管壁脂联素的阳性表达强度(2+)弱于正常组(3+),经药物干预后,各干预组血管壁脂联素的阳性表达强度均明显增强,其中预用益脑康组血管壁脂联素的阳性表达强度(4+)高于益脑康组和立普妥组(3+)。说明益脑康胶囊和立普妥在改善模型鼠胰岛素抵抗状态的同时,增加了血管壁脂联素的表达。且预用益脑康组增强明显,说明预防用药效果显著。
     脑组织病理检测显示:治疗结束后,复合模型组脑组织水肿加重,炎症明显。干预各组跟同期复合模型组相比,皮质层神经元修复明显,炎症消失,水肿减轻,其中预用益脑康组比益脑康组神经元修复和水肿减轻明显,提示预防用药治疗急性缺血中风效果显著。
     脑组织含水量,预用益脑康组、益脑康组、立普妥组均较复合模型组下降,但三组之间比较无统计学意义。
     结论
     临床部分:中医综合治疗方案可以改善急性缺血中风合并糖尿病阴类证患者的神经功能缺损程度,减轻残障水平;可以降低治疗后的中医症征积分;提高患者生活能力;随着随访时间的延长,中医综合治疗方案有提高患者生存质量的趋势。
     实验部分:益脑康胶囊能降低急性缺血中风大鼠游离脂肪酸水平,且预用益脑康效果显著;降低胰岛素抵抗指数;提高模型鼠颈动脉脂联素的阳性表达,预防用益脑康效果优于短时间用药;改善大鼠脑组织水肿,修复受损脑组织皮质神经元,减轻血管周围水肿。实验结果表明益脑康胶囊可能是通过改善急性缺血中风大鼠的胰岛素抵抗来发挥其治疗作用的,且预防用药效果优于短时用药。
Background
     Stroke is known as "the first killer of human health", with high prevalence, high mortality, high morbidity and high recurrence rate. It is a serious public health problem of global issues. Cerebrovascular disease is the second cause of death in China, of which 1/3 of the patients died, the other 1/3 of patients had permanent disabilities, increasing burden considerably to social and family.
     Studing on stroke disease risk factors for treatment and prevention of stroke is the first question, by controlling these risk factors to prevent stroke. Diabetes is a major risk factor for stroke and one of the independent risk factor for atherosclerotic cerebrovascular disease. So treating cerebral infarction from the risk factors, and exploring its possible mechanism which is an important way to reduce the morbidity and mortality, improve quality of life and to prevent recurrence. Chinese medicine have unique advantages in the treatment of stroke. A comprehensive treatment program can obtain the best results, when we face the storke patients of many critical clinical syndrome. The comprehensive treatment based on traditional Chinese medicine consists of including yinaokao capsule, Huatuozaizao pill and Fleabane injection.
     Purpose
     This study was designed to retrospectiviy analysis of the database by using a variety of statistical methods. Discussing the therapeutic effect of the comprehensive treatment based on traditional Chinese medicine for acute ischemic stroke patients with diabetes mellitus for neurologic impairment, disability, activities of daily living, traditional Chinese Medicine Syndrome and Symptoms. We copy the rat model of acute ischemic stroke based on atherosclerosis through animal experiments, and assess it from the behavioral, biochemical, immunohistochemistry and pathology; Mainly abserving the effect of Yinaokang capsule on blood biochemical parameters about insulin resistance and adiponectin levels, expression of adiponectin in vascular wall and pathological changes in brain tissue. We try to explain the possible action mechanism about Yinaokao capsule treating acute ischemic stroke from the insulin resistance.
     Method
     Clinical research:We analyzed retrospectively the database by the statistical analysis software SPSS13.0. Observing the effect of acute ischemic stroke patients with diabetes and without diabetic in the group of treated by the comprehensive treatment based on TCM. The effect consists of the level of neurological impairment, disability level, ADL, BI, their stroke symptom of TCM. Observing the effect of the acute ischemic stroke patients with or without a history of diabetes treated by the compretensive treatment based on TCM or Western medicine treatment. We discuss the effect of the compretensive treatment based on TCM for acute ischemic stroke with diabetes for their stroke symptom of TCM, the level of neurological impairment, disability level, BI, ADL.
     Animal experiment,115 rats were randomly divided into normalcontrol group, atherosclerotic group, compound model group, the Yinaokang capsule prevention group, Yinaokang capsule treatment group, Atorvastatin Calcium capsule treatment group., We replicate the rat models of atherosclerosis by feeding them high fat diet, then copy the ischemia model based on atherosclerosis rate models. Evaluating the model from the behavioral, biochemical, pathological and other aspects. We give Yinaokang Capsule to the the Yinaokang capsule prevention group in advance, and Yinaokang Capsule, Atorvastatin Calcium capsule to the other groups in normal treatment time. We evaluate the effect of the Yinaokang Capsule treatment from the behavior (Zea Longa neurological evaluation score), biochemical (glucose, insulin, adiponectin, free fatty acids, and calculated insulin resistance index), immunohistochemistry (adiponectin expression level in carotid artery expression), brain pathology, brain water content and so on. We try to explain the possible action mechanism about Yinaokao capsule treating acute ischemic stroke from the insulin resistance.
     Result
     Clinical part:For the comprehensive treatment based on TCM group with diabetes and non-diabetic patients of acute ischemic stroke after treatment, Results:There is no significantly difference in neurologic impairment, disability level, activities of daily living, Stroke symptom score of TCM between the two groups patients(P>0.05). After treated by the comprehensive treatment based on TCM or western medicine treatment for the acute ischemic stroke patients with diabetes. We can obtain that there are significant differences in decline, with statistically significant (P<0.05), compared with the baseline NIHSS score in the first 21 days for the degree of neurological impairment scores. There is significant difference between the GOS score (p<0.05) for disability levels between two groups in 21 days; BI index is not significant difference (P>0.05) on the first 21 days, following 60 days and 90 days;Stroke syndrome of TCM about life in 21 days,90 days has the statistically significant difference (P<0.05).
     It is seen that the comprehensive treatment based on TCM can improve neurologic impairment; to reduce the level of 21-day disability; to reduce the 90-day ADL after treatment;to reduce the 21-day and 90-day SSTCM; to improve the living capacity of patients up to 90 days; There is the trend of improving the quality of life of patients treated by the comprehensive treatment based on TCM. It is worth further research to the comprehensive treatment based on TCM.
     Experimental part:We feed the rats high fat diet to induce hyperlipidemia-insulin resistant rats, based on which reproducing the acute ischemia-reperfusion rat models in this study, which according to the pathogenesis of human ischemic stroke. Yinaokang capsule can reduces the blood glucose level, insulin level, insulin resistance index of the rat models compared before and after treatment; Atorvastatin Calcium capsule can reduce the insulin levels of the rat model, both medicines have little effect on the level of adiponectin. Atorvastatin Calcium capsule can reduce the level of free fatty acid of the rat model;the Yinaokang capsule prerusing can reduce the level of free fatty acids in rats. Three treatment groups are compared with eath other. The effect of Yinaokang capsule is better than Atorvastatin Calcium capsule for reducing the level of blood glucose. There is no significant difference between the three groups eath other in reducing insulin levels, insulin resistance index, adiponectin. The preusing Yinaokang effect of the reduction of free fatty acids better than the Atorvastatin Calcium capsule. no significant differences.
     Adiponectin Immunohistochemistry of the rats'carotid artery showes that positive adiponectin expression (2+) in the rats'vascular wall of compound model group weaker than the normal group (3+) before treatment. The positive expression of adiponectin is significantly increased strength than before in all of intervention groups after drug intervention. Expression of adiponectin in strength (4+) of the perusing Yinaokng group more strong than the other groups (3+) among them. We can see that Yinaokang capsule and Atorvastatin Calcium capsule can increase the expression of adiponectin in vascular wall, while improving insulin resistance of the rat model, And the expression of adiponectin of preusing Yinaokang group is enhanced more significantly than the other two groups.
     Pathological examination of brain tissue showed:the brain tissue of composite model group has serious edema and inflammation after treatment. There are significant cortical neurons repaired, inflammation disappeared, edema alleviated for intervention groups which compared with composite model in the same time. The effect is more better of perusing Yinaokang group than Yinaokang group, which suggests that preventive treatment of acute ischemic stroke effect is remarkable.
     Brain water content of the three intervention groups is decreased than of composite model group. But there is no statistical significance among the three groups.
     Conclusion
     Clinical part:The comprehensive treatment of TCM can improve neurologic impairment degree, reduce disability levels, improve life ability, reduce SSTCM of the acute ischemic stroke with diabetic patients; The comprehensive treatment of TCM can improve the quality of life of patients with the trend.
     Experimental part:Yinaokang capsule can reduce the free fatty acid levels of ischemic stroke rats, and pre-using Yinaokang group'effect more better; Yinaokang capsule can significantly reduce the insulin resistance index, improve the adiponectin expression of the rats'carotid, improve the brain issue edema, repair the damaged cortical neurons of brain, and reduce the perivascular edema. The experiment results show that the treatment effect of Yinaokang by improving insulin resistance state, and prevention of drug better than the short-term medication.
引文
[1]李志.针刺对急性脑梗死合并血脂异常患者血脂水平的影响[J].中医药学刊,2006,24(4):744.
    [2]王永炎主编.中医内科学.第一版,上海科学技术出版社,1997:124.
    [3]王永炎,刘炳林.中风病研究进展评述.中国中医急症,1995,2(4):51-53.
    [4]刘强,高颖.中风病不同阶段四诊信息的指标聚类分析.中华中医药杂志,2007,22(3):162-164.
    [5]马斌,高颖.中风病发病第7天证候要素的初步分析.中国中医基础医学杂志,2006,12(7):494-496.
    [6]刘茂才,黄培新,梁伟雄,等.高血压性中、大量脑出血救治方案建立的思路.广州中医药大学学报,2001,18(1):1-4.
    [7]卢明,杜宝新,等.对中风病急性期以阴阳辨证代替传统九型辨证的可行性临床验证.广州中医药大学学报,2006,23(4):279-231.
    [8]郦永平.脑梗塞中医辨证现代化初探一311例回顾性临床资料分析[J].中国中医急症,2000,9(8):264—265.
    [9]黄燕,杨利,蔡业峰等,出血中风和缺血中风病机差异与“脑中血海”“升降枢轴”的关系初探.中国中医药信息杂志2004,(11)6:472-473
    [10]蔡业峰,付于,等.中医药治疗急性缺血中风的多中心随机对照研究.中材,2007,30(9):1192-1195.
    [11]王国华,陈炯华.中医药治疗脑梗塞研究摄要.中医药学刊,2004,22(1):98-100.
    [12]刘黎明,魏爱环.祛瘀通络方治疗脑血管病脑梗死170例.陕西中医,2009,30(7):822-823.
    [13]王永炎,孙塑伦,等.辨证论治加复方活血注射液治疗中风急症的临床研究[J].北京中医学院学报,1988,11(1):22~24.
    [14]余以本,马卫琴.加昧温胆汤治疗风痰阻络型脑梗塞50例疗效观察.福建中医药,2009,40(1):10-11.
    [15]郑绍忠,中药及其有效成分治疗脑梗塞的现代药理研究进展.海峡药学,1998,10(3):9-11.
    [16]郑关毅,张景寿.补阳还五汤治疗脑梗塞的疗效及其机制探讨.中西医结合临床实用急救,1997,4(6):256-258.
    [17]崔淑萍.血栓通与舒血宁联合治疗脑梗死60例.陕西中医,2009,30(10):1313-1314.
    [18]陈康宁,董为伟.灯盏花注射液对脑缺血损伤的防治研究.中国中西医结 台杂志,1998,18(11):684-686.
    [19]李崖雪,黄晓媛.头针双区丛刺法治疗脑梗死临床观察.上海针灸杂志,2005,24(8):28-29.
    [20]曹银香,白炜玮.眼针治疗脑梗死半身不遂156例临床观察.河北中医,2008,30(3):286-287.
    [21]张明波,张霆.眼针疗法对缺血性中风血液流变学影响的研究[J].辽宁中医杂志,1997,24(5):232—233.
    [22]曾贤.针刺穴位注射治疗中枢性偏瘫疗效观察.辽宁中医学院学报,2005,7(3):259-260.
    [23]穆艳云,李忠仁,等.针刺对急性脑梗死患者血清IL-6、IL-8影响的观察.上海针灸杂志,2008,27(11):3-5.
    [24]唐胜修,徐祖豪.针灸治疗脑梗塞的临床研究进展.2002,21(4):544-546.
    [25]欧阳珊,王可嘉,等.中国六城市多种危险因素对脑血管病影响的分析.中风与神经疾病杂志.1991,8(3):153.
    [26]陶国枢.老年流行学概述(下).人民军医保健专刊,1995,(2):5.
    [27]杨丽平,王路琰.短暂性脑缺血发作与脑缺血耐受[J].国外医学·脑血管疾病分册,2004,12(4):282—284.
    [28]赵钛.现代偏瘫治疗学.第1版,人民军医出版社,1996:4-56.
    [29]Kim JS. Yoon SS, lee SI, et al. Type A behavior and stroke:high tenseness dimension may be a risk factor for cerebral infarction. Eur Neurol,1998; 39(3):168—173.
    [30]Kiyohara Y, Kato I, lwamoto H, et al. The impact of alcohol and hypertension on stroke incidence in a general Japanese population. The Hissayma Study. Stroke,1995; 26(3):368—372.
    [31]Gorelick PB, Harmaen P. Abbott RD, et al. Is acute alcohol ingestion a risk factor for ischemic stroke? Results of controlled study in middle-aged and elderly stroke patients at three urban medical centers. Stroke,1987:359—364.
    [32]徐卫历,汪培山,等.饮酒与脑出血和脑梗塞关系的比较.中华临床医药,2001,2(3):29-31.
    [33]沈丽,卢维晟,等.不同方法建立动脉粥样硬化大鼠模型的比较.心脏杂志,2005,Ⅰ7(1):18-20.
    [34]高奋,李静梅,等.高同型半胱氨酸血症兔模型动脉粥样硬化的形成.中国动脉硬化杂志。2002,10(4):348.
    [35]张勇,娄桂予,钱民章.建立兔高脂血症模型及动脉粥样硬化斑块的方法.遵义医学院报,2001,24(8):304.
    [36]郭延松,吴宗贵.鼠动脉粥样硬化模型复制方法的比较.中国动脉硬化杂志。2003,11(5):465.
    [37]马杰,郭力辉,等.鹌鹁动脉粥样硬化模型的探讨.动物学杂志,1997,32(2):19-21.
    [38]李秋梅,王硕仁,等.家兔新型动脉粥样硬化狭窄模型的建立及其动态观察.中国实验动物学报,2004,12(1):26-28.
    [39]姜炜,郭阳.颈动脉内膜切除术后再狭窄动物模型的建立.天津医药,2007,2(35): 2.
    [40]Cottin Y, Kollum M, Kolodgie FD, et al. Intravascular radiation accelerates atherosclerotic lesion formation of hyperc-holes— terolemic rabbits. Cardiovasc Radlat Med,2001,2(4):231—240.
    [41]Joen RS, Ching HW. Mechanisms in the inhibition of neointimal hyperplasis with triflavin in a rat model of balloon angioplast3. J Lab Clin Med,2001,13(4):270.
    [42]吴开云,高摄渊.移植胚胎鼠弓状核细胞后对动脉粥样样硬化形成的影响.中国动脉硬化杂志,2000,8(2):118.
    [43]孙文清,杨永宗,等.小型猪动脉粥样硬化斑块稳定性模型研究.全国医学理论与实践,2006,6(1):6.
    [44]Hofmarm SL, Russell Dw. Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice. Science,1988, 239:127.
    [45]Plump AS, Smith JD. Severe hypereholes lerolemin and atheroselerosis in apolipoprotein E-deficient mice erealed by homologous recombination in ES cells. Cell,1992,71:343.
    [46]张瑞华,余竹元,王卫群,等.肺炎衣原体感染与动脉粥样硬化动物模型研究新进展.海峡预防医学杂志,2002,8(3):31-32.
    [47]Rubin EM, Isbids BY. Expression of human apolipoprotein A-1 in transgenic mice results in reduced plasma new high density lipoprotein size subclasses. Proc Natl Acad Sci USA,1991,353:265.
    [48]闫盛,郝斌.动脉粥样硬化动物模型研究现状.山西医药杂志,2008,37(8):731-733.
    [49]王志萍,曾因明.线栓法制备大鼠局灶性脑缺血再灌注模型的研究进展.《国外医学》麻醉学与复苏分册,2005,26(3):144-146.
    [50]顾国军,黄振兴,陶凯忠等.HBO-1对内皮素-1诱导的大鼠局灶性脑缺血模型的疗效观察.第二军医大学学报,2006,27(10):1134-1137.
    [51]Biernaskie J, Corbett D, Peeling J, et al. A serial MR study of cerebral blood flow changes and lesion development following endothelin-1 — induced ischemia in rats[J]. Magn Reson Med,2001,46:827-830.
    [52]Sharkey J, Ritchie IM, Kelly PA. Perivascular microapplication of endothelin-1:a new model of focal cerebral ischaemia in the rat[J]. J Cereb Blood Flow Metab,1993,13:865—821.
    [53]管玉龙.胰岛素抵抗与冠心病.心肺血管病杂志,2000,19(3):239-241.
    [54]龚兵.2型糖尿病急性脑梗死85例临床分析.医学创新研究,2007,35(4):71-72.
    [55]陈丹杰,杨华章.2型糖尿病合并脑梗塞危险因素分析.实用医学杂志,2003,19(5):521-522.
    [56]史洪润,杨长庆,等.高血糖时红细胞聚集与急性脑梗塞关系的研究.中风与神经疾病杂志,1999,16(3):159.
    [57]Beamer N, Giraud G, Clark W, et al. Diabetic hypertension and erythrocyte aggregation in acute stroke, Cerebrovasc Dis,1997,7(1): 144.
    [58]声雪玲,蒋升,谢自敬,等.2型糖尿病动脉粥样硬化的危险因素分析.新疆医学,2005,35(2):7-9.
    [59]Josephine M Forbes. et al. AGE promotes the atherosclerosis of T2DM. Diabetes 2004,53:1813—1823.
    [60]叶爱娇,孙军.老年2型糖尿病脑动脉狭窄相关性危险因素分析.浙江临床医学,2007,9(10):1313-1314.
    [61]Faleone C, Nespoli L, Ceroldi D, et al. Silent myocardial ischernia in diabetic and nondiabetic patients with coronary artery disease, Int J Cardiol,2003,90:219-227.
    [62]陆浩.高胰岛素血症与动脉粥样硬化.中国临床医学,2008,15(1):35—38.
    [63]郑艳宇.急性脑梗塞患者血浆胰岛素水平动态观测及临床意义中华医学实践杂志,2003,2(11):995—996.
    [64]薛慎伍,葛树业,等.急性脑梗塞患者血浆内皮素与病灶大小、部位病程的关系.临床神经病学杂志,1998,11(1):31-32.
    [65]管玉龙.胰岛素抵抗与冠心病.心肺血管病杂志,2000,19(3):239-241.
    [66]沙榆波,施龙华.2型糖尿病合并脑梗塞的临床分析.辽宁实用糖尿病杂志,
    2004,12(11):32-33.
    [67]高兰霞.胰岛素抵抗与糖尿病慢性并发症(综述)。中国城乡企业卫生,2007年10月第5期:36-38
    [68]杜天敏.糖尿病合并高脂血症42例临床分析,中国实用内科杂志,2000,20(5): 195.
    [69]陈丹,路学荣,张跃春.糖尿病合并脑梗死42例血脂代谢异常分析.中国实用内科杂志,2002,22(6):355.
    [70]林海,付丽佳,卢立春,等.糖尿病性脑卒中88例分析.中国实用内科杂志,2002,22(4):242.
    [71]郭瑜健,陈生弟.胰岛素抵抗与缺血性脑血管病.国外医学(脑血管疾病分册),1998,6(1):28.
    [72]陈阳,帅杰.高血糖与脑缺血.国外医学(脑血管疾病分册),2002,10(3):217.
    [73]帅杰.葡萄糖毒性与脑缺血损害.脑与神经疾病杂志,2003,11(1):30.
    [74]Scherer PE, Williams S, Fogliano M, et al. Anovel serum protein similar to Clq, produce dexclusively in adipocytes. J Biol Chem,1995,270(45): 26746—26749.
    [75]Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose specificprotein r adiponectin, inobesity. Biochem Biophys Res Commun, 1999,257(1):79—83.
    [76]Goropashnaya AV, Herron J, Sexton M, et al. Relationships between plasma adiponectin and body fat distribution, insulin sensitivity, and plasma lipoproteins inAlaskan Yup'ik Eskimos:the Center for Alaska Native Health Research study[J]. Metabolism,2009,58(1):22-29.
    [77]Mao X, Kikani CK, Riojas RA, et al. APPL1 binds to adiponectin receptors and mediates adiponectin signaling and function [J]. Nat Cell Biol,2006, 8(5):516-523.
    [78]Yoon MJ, Lee GY, Chung JJ, et al. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP— activated protein kinase, p38 mitogen—activated protein kinase, and peroxisome proliferatoractivated receptor [J]. Diabetes,2006,55(9): 2562-2570.
    [79]刘军,姚庆姑,许火根,等.代谢紊乱患者脂联素水平和颈动脉粥样硬化的研究[J].临床内科杂志,2004.21(10):684—686.
    [80]Murakami H, Ura N, Furuhashi M, et al. Role of adoponectin in insulin — resistant hypertension and atheroselerosis[J]. Hypertens Res,2003, 26 (9):705—710.
    [81]Kato H, Kashiwagi H, shiraga M, et, al. Adiponectin act as an endogenous antithrombotic factor[J]. ArteriOscler Thromb Vase Biol,2006,26(1): 224—230.
    [82]Ouchi N, Kihara S, Anta Y, et al. Adipeyte-derived plas-ma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expres-sion in human mo noeyt e-derived macrophages. Circulation,2001,103:1057-1063.
    [83]徐昶,周强,马业新.脂联素与冠心病及其危险因素关系的研究进展.中国动脉硬化杂志,2008,16(2):158—160.
    [84]肖书平,黄培新,雒晓东中风病综台治疗研究述评.中国中医药信息杂志,2001,8(1):14.
    [85]肖书平,黄培新,雒晓东.脑梗塞急性期中医综合治疗对比研究.中国中医急症,2002,11(3):160-161.
    [86]黄培新,黄燕,卢明,等.急性脑出血中西医结合综合治疗方案研究[J].中国中西医结合杂志,2006,26(7):590-593.
    [87]Renard C, Van Obberghen E. Role of diabetes in atherosclerotic pathogenesis. What have we learned from animal models?[J]. Diabetes Metab, 2006,32:15-29
    [88]Ugoya OS, Ugoya AT, Agaba IE, et al. Stroke in persons with diabetes mellitus in Jos. Nigeria[J]. Niger J Med,2006,15:215—218
    [89]Giorda CB, Avogaro A, Maggini M, et al. Incidence and risk factors for stroke in type 2 diabetic patients:The DAI Study[J]. Stroke,2007, 38:1154—1160
    [90]Bravata DM, Wells CK, Kernan wN, et al. Association between impaired insulin sensitivity and stroke[J]. Neuroepidemiology,2005,25:69—74.
    [91]刘巧玲,俞德彩,张丽娟.血糖水平对进展性卒中的影响[J].现代医药卫生,2007,23:1274-1275.
    [92]郭朝英.糖尿病合并脑卒中病情及预后的探讨.中国民族民间医药,2009,4:30-31.
    [93]许文灿,陈慎红,陈永松,等.糖尿病并脑坏死的发病和预防与血脂的关系.医师进修杂志,2005,28(1):32.
    [94]Megherbi SE, Milan C, Minier D, et al. Association between diabetes and stroke on survival and functional outcome 3 months after stroke: data from the European BIOMED[J]. Stroke,2003,34:688-694
    [95]Kaarisalo MM, Raiba I, Sivcnius J, et al. Diabetes worsens the outcome of acute ischemic stroke[J]. Diabetes Res Clin Pract,2005,69:293— 298
    [96]翁维良,崔晶.华佗再造丸对脑血管病人血液流变性影响的观察.实用中西医结台杂志,1990,3(5):305
    [97]高俊发,张秀英.华佗再造丸对糖尿病患者血液流变学影响.时珍国医国药.1999,10(7):489
    [98]魏江磊.华佗再造丸临床效应的比较研究.中成药,1995,17(1):22
    [99]杜光明,李喜枝,赵红缨,等.华佗再造丸对太鼠SOD、NDA影响的实验研究.西南国防医药,1993,3(6):367
    [100]刘兴华.灯盏细辛注射液治疗脑梗死30例[J].中国中医急症,2005,14(12):1227
    [101]李娜,姜义,孙海欣,等.灯盏细辛注射液治疗急性脑梗死有效性的临床研究.首都医科大学学报,2008,29(3):336-339
    [102]LIU H, YANG X, ZHOU L, et al. Study on effects scutellarin on scavenging reactive oxygen [J]. Chinese Materia Medica,2002,25(7):491—493.
    [103]沈丽,卢维晟等.不同方法建立动脉粥样硬化大鼠模型比较,心脏杂志.2005.10(1):18-20.
    [104]杨鹏远,芮耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立.第二军医大学学报,2003,7(24):7.
    [105]顾国军,黄振兴,陶凯忠等.HBO-1对内皮素-1诱导的大鼠局灶性脑缺血模型的疗效观察.第二军医大学学报,2006,27(10):1134-1137.
    [106]Zea Longa EL, Weinstein PR, Carlson S, et al. Reversible midle cerebral artery occlusion without craniectomy in rats. Stroke.1989,20:84-91.
    [107]程中荣,王旭光.胰岛素抵抗与游离脂肪酸.中国社区医师,2008,10(18):10-11
    [108]张亚文,丁德民.游离脂肪酸与胰岛素抵抗[J].天津医科大学学报,2004,10(1):144-146.
    [109]陈辉,涂植光.胰岛素抵抗中游离脂肪酸的作用[J].国外医学:临床生物化学与检验学分册,2003,24(6):316-317.
    [110]Rashids, Watanabe T, Sakaue T, et al. Mechanisms of HDL lowering in insulin resistant. hypertriglycerdemic states:Ihe combined efect Of HDL triglyeeride enrichment and elevated hepatic lipase activity. Clin Biochem.2003; 36(6):421-425.
    [111]吴浩,吉训明,赵喜庆.改良大鼠MCAO模型的建立.中华实验外科杂志,2006,23(12):4553-4554.
    [112]Sharkey J, Ritchie IM, Kelly PA. Perivascular microapplication of endothelin-1:a new model of focal cerebral ischaemia in the rat[J]. J Cereb Blood Flow Metab,1993,13:865—821.
    [113]顾国军,黄振兴,等.HBO对内皮素—1诱导的大鼠局灶性脑缺血模型的疗效观察.第二军医大学学报,2006,27(10):1134-1137.
    [114]Biernaskie J, Corbett D, Peeling J,et al.A serial MR study of cerebral blood flow changes and lesion development following endothelin-1— induced ischemia in rats[J]. Magn Reson Med,2001,46:822-830.
    [115]中华医学会全国高血压、冠心病与糖尿病专题研讨会纪要.中华心血管病杂志,1993,21:26.
    [116]Reaven GM Syndrome x:6 years latter. J Internal Med 1994; 236(Suppl736):13
    [117]李雪英,孙向阳,韩金芹.2型糖尿病胰岛素抵抗的病因病机与证治探讨.中医药临床杂志,2009,21(4):355-356
    [118]高美风,黄容,陈云芳.黄芪多糖的提取及其治疗糖尿病药理作用进展.辽宁中医药大学学报,2008,10(6):38-41
    [119]纪云西,蒋历.胰岛素抵抗的中医病机实质探析(J].辽宁中医药大学学报,2008,10(3):23—24.
    [120]余亚信,李学军,杨叔禹.活血化瘀法治疗胰岛素抵抗相性疾病随机对照试验的系统评价.光明中医,2009,24(7):1216-1219.
    [121]莫可元,张桂英,莫志江.水蛭的药理研究进展[J]中成药,2003,25(5):408—410.
    [122]李艳玲,黄荣清,崔玉芳,等.水蛭的研究概况及展望[J].科学技术与工程,2004,4(3):239—243.
    [123]蔡业峰,付于,等.中医药治疗急性缺血中风的多中心随机对照研究.中药材,2007,30(9):1192-1195.

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