【作者】 葛峥；

【导师】 施旭光；

【作者基本信息】 广州中医药大学 ， 方剂学， 2006， 硕士

【摘要】 类风湿性关节炎(rheumatoid arthritis,简称RA)是一种慢性、炎性、系统性的自身免疫性疾病,临床主要特征为局部关节肿痛,晚期可引起关节的僵直、畸形和功能严重受损。该病在世界范围内普遍存在,具有病程长、缠绵难愈、致残率高且又易于复发等特点,严重威胁人类的健康和生活质量,所以本病的临床治疗是多年来众多学者孜孜以求却又一直难以实现飞跃的棘手问题。 RA病理机制目前还不清楚,所提出的种种观点只能解释部分临床表现。但是越来越多的学者已逐渐达成共识——免疫系统的紊乱和本病息息相关。许多研究已经表明淋巴细胞、中性粒细胞、巨噬细胞、滑膜细胞等多种炎症细胞介导的异常细胞免疫、体液免疫,导致关节局部和全身的免疫功能紊乱,在RA的病理中起着重要作用。 乌头汤是东汉时代著名医学家张仲景创制的一首名方,该方由制川乌、黄芪、麻黄、芍药、炙甘草所组成,具有温经散寒,祛湿止痛的功效,主治寒湿痹证。经过以往的临床应用和动物实验证实本方对RA具有明确肯定的治疗作用,具有一定的镇痛作用,具有抗急、慢性炎症作用,其中对急性炎症的抗炎效果较好。但是关于本方的配伍规律及更深的实验研究的文献并不多见,本课题主要通过乌头汤的撤药拆方的研究,观察其细胞因子、血液流变学、T淋巴细胞亚群及免疫器官等药理药效学指标,一方面探讨乌头汤的配伍规律,揭示、论证前人组方的基本理论,另一方面也为本方的临床加减运用以及改造原方,创制更有效的新方提供依据。 本课题研究结果: 1、对血清中细胞因子检测结果表明:乌头汤及其配伍各组均能不同程度的抑制AA大鼠血清中分泌较高的IL-1β、TNF—α含量,尤其是乌头汤全方组药效更明显,与模型组相比差异有显著性意义。提示乌头汤及其各配伍组可以不同程度的阻止滑膜成纤维细胞的过度增殖,在细胞因子网络水平上发挥免疫调控作用达到抗类风湿关节炎的目的。 2、从血流动力学改变显示:与模型组相比,乌头汤及其各配伍组对大鼠血液流变学呈现多方面的影响,具体表现为能降低红细胞压积和血浆粘度,同时降低红细胞聚集指数,从而呈现出全血粘度和全血还原粘度下降。提示乌头汤可以改善血液呈现的高凝和高粘状态,促进和恢复微循环的正常状态,增加肢体营养,减轻肢体损伤,从而发挥抗类风湿性关节炎的综合作用。 3、从对外周血中T淋巴细胞亚群的调节来看:模型组的大鼠外周血中CD4~+细胞的百分比含量明显升高,CD8~+细胞的百分比含量明显降低,同时CD4~+与CD8~+的比值表现为升高的趋势。乌头汤及其各配伍治疗组可以对外周血中混乱的T淋巴细胞亚群更多还原

【Abstract】 Rheumatoid Arthritis (RA) is a sort of chronic , inflammational , systemal disease of self-immunity , with mainly clinic characterizes as local-arthritis pain , terminal result can be ankylosis monstrosity and even function invalidate with joints . This disease is ubiquity all aroud the world , have the characterizes such as : long course of disease , diffcult to cure totally , have high cripple rate and hard to reoccur . Threaten human health and live quality severity , So the treatment of this disease is a problem that many professors work hard on and also a problem that is very difficult to solve .The reason and the mechanism of the disease are not very clear yet , and all the opinions that were put out can only explain part of the symptoms . But more and more professors have the same opinion that the disorder of the immune system has close relations with the disease . Many researches have already been indicated that lymphocyte , neuter- granulocyte , macrophage cell , slide-checa cell etc. multi-inflammational cells lead to abnormal cellularital immunity and body-fluid immunity , finally make for immunity dysfunction of part- arthrosis and systemic , its plays an importance role in course of pathology of RA .Wutou Decoction is a famous prescription created by a famous doctor named Zhang Zhongjing in Dong Han age , this prescription is comprised by Aconite , Astragalus , Ephedra , Peony and Roast-liquorice , have the efficacy of warm venation so that dispel cold , drive away damp and alleviate pain , it can mainly treat arthralgia syndromes caused by cold and damp . According to previously clinical experiences and animal experiments of these years , it proved that this prescription has doubtless cure function on anti- rheumatoid arthritis . it has a certain extent of ease pain , has the function of anti-acute or chronic inflammation , especially for acute inflammation . The study about Wutou Decoction on prescription rules and further animal experiment are very poor , this study observed pharmacology target such as cytokine , hemorrheology , T-lymphocyte clusters and immunity organ . So one hand we can reveal the compatible rules of Wutou Decoction , demonstration the existed theory , on the other hand the reacher can provide for modification of prescription , improve the original prescription and create more effective prescription . The result of this experiments indicate that :1 The effects of cytokine content in AA-rats’ blood serum : Wutou Decoction group and its prescription groups can reduce the cytokine (IL—1 ., TNF— a)content in AA-rats’ blood serum , the drug effect is especially good in Wutou Decoction group , the different compared with model group has a remarkable significance . It indicate that Wutou Decoction group and its prescription groups can prevent slide-checa fibroblast excess multiplication on differ degrees , so they can exert immune adjust function on network level of cytokine , in this way , achieving the aim that anti- rheumatoid arthritis .2, The changes in hemorrheology of AA-rats : Compared with model group , the influence of traditional Chinese medicine treaty on hemodynamics embody in many aspects of Wutou Decoction group and its prescription groups . On the one hand, it is able to reduce the hematocrit and plasma viscidity notably , On the other hand , it can reduce the the index of red blood corpuscles togather,thus demonstrate the whole blood viscidity and whole blood reduce viscidity to drop . Indicate that Wutou Decoction can reduce blood high-curdle and high-thick , remove blood stasis , improve and resume tiny-circulation , increase body nutrition , lighten system trauma , so that play anti- rheumatoid arthritis function .3^ T-lymphocyte clusters (CD4+ and CD8+) content in AA-rats blood measure result indicates : In model group , the percent of CD4+ in AA-rats blood is evidencely increased , the percent content of CD8+ cell is reduce , at the same time , the rates between CD4+ and CD8+ have the trend of increase . Wutou Decoction group and its prescription groups can play differ effects on T-lymphocyte clusters (CD4+ , CD8+ and CD4+/CD8+) , as a result , restrain the over-excited cellularital immunity .4s From the immunity organ aspect , we can see in the course of anatomise ,with naked eye , Thymus gland and spleen of model group rats have differ degree hyperemia , and even in some rats , there spleen tumescence and thymus gland atrophy are very seriously . After therapyed with Wutou Decoction group and its prescription groups , the damage in immunity organ can be lighted in differ degrees , so we can confer , Wutou Decoction can resume the immunity function , anti- rheumatoid arthritis from fundamentality .5> About this prescription rules : Wutou Decoction group and its prescription groups all can manifest different degree function of anti-inflammation , adjust immunity, activating blood flow . But on the whole , the curative effects of prescription groups are less than Wutou Decoction group . Compare to Wutou Decoction group , there are no obvious difference . It not only shows the rationality of forming prescription of Wutou Decoction , but also the correctness of prescription compatibility theory . There are no obvious differences between Wutou Decoction group and prescription groups , the mostly causes may be : Firstly, modern pharmacology researches show , each herbal medicines in perscription have definite function of anti-inflammation and analgesis , moreover , Astragalus has bidirection of adjust immunity function . All these may be one reason of cause no obvious different between Wutou Decoction group and its prescription groups . Secondly , it also may be we made animal model does not according to the theory of Traditional Chinese Medicine . As the theory of TCM , Wutou Decoction has the function of treat arthralgia syndromes caused by cold and damp , it arises relate to outside environment and depressed body immunity function . But our study is a disease model of modern medicine , it does not aim at pathogeny and pathology of TCM . But each prescription group has a certain extent effect , it also show that every herble medicine has take part in the whole function , the result is the reciprocity of all herble medicines cooperate with each other together.Synthesizing the former results , Wutou Decoction have good effect of anti-rheumatoid arthritis , its function mechanism is a multi-approaches and multi-points synthetical-effect result . This study is just a begin , we hope more researches appear with further level .更多还原