【作者】 张云；

【导师】 吕广能；

【作者基本信息】 四川大学 ， 生理学， 2003， 硕士

【摘要】 重症肌无力(myasthenia gravis，MG)是一种自身免疫性疾病，其主要表现为肌收缩无力，易疲劳。目前，用激素等免疫抑制剂治疗MG仍是主要方法之一，但其副作用明显且不易消除，使临床工作者治疗MG受到一定程度的困扰。近年来，大量研究已经证实雷公藤多甙(Tripterygium Wilfordii Polyglycosidium，TWP)具有明确的抗炎、免疫抑制作用，且临床研究也已显示其治疗MG效果好、毒副作用少，是治疗MG安全有效的药物，其避免了糖皮质激素及细胞毒性药物所引起的难以克服的毒副作用，其作用范围及作用疗效日渐被人们所重视，但其具体作用机制，到目前为止还不是十分清楚。本课题组前面的研究发现，TWP能通过提高神经-肌接头处兴奋传递，增强肌肉的收缩。但是，TWP对肌收缩本身是否有影响，尚存在疑问。而且，TWP治疗MG的药效学作用的客观参数和依据，鲜有报道。因此，本实验的目的是深入探讨TWP的药理作用，及其可能的作用机制，为反映TWP的药效提供一个客观方法和客观依据，并为临床应用TWP治疗MG提供直接的实验和理论基础。 本研究分两部分内容： 第一部分：用电生理学方法，研究TWP对蟾蜍腓肠肌收缩张力的影响。研究结果表明： 1．TWP不仅可促进神经-肌接头间兴奋传递，还可直接增强肌四少11大学硕士学位论文肉本身的收缩力。2.溶剂二甲亚酚(DMSO)对肌收缩本身有抑制作用 第二部分:利用从小牛肌肉组织提取的AchR作为抗原，免疫C57BL/6小鼠，建立实验性自身免疫性重症肌无力(experimentalautoimmune myas出enia盯avis，EAMG)动物模型;用电生理学方法检测TWP对EANIG动物模型排肠肌和旋前圆肌复合动作电位的影响。研究结果表明: 1.EAMG动物模型建立成功。 2.TWP可增大EAMG动物胖肠肌和旋前圆肌复合动作电位的幅度。 3.TWP对不同肌肉间复合动作电位的影响没有差异。 4.TWP可能不仅通过促进神经一肌接头间兴奋传递，还通过其它作用机理，联合作用增加肌肉复合动作电位幅度。 5.检测多组神经肌肉肌电图，可提高MG诊断阳性率。更多还原

【Abstract】 Myasthenis gravis (MG) is an autoimmune disease. It manifestsitself by varying weakness of muscle under voluntery control. Prednisone is one of the most effective treatments for MG. However, it has relatively severe side effects. A great deal of researchs has confirmed that Tripterygium Wilfordii Polyglycosidium (TWP) has strong anti-inflammatory and immunosuppressing effect. Clinical researchs have showed that TWP is a kind of safe and effective herb medicine in treating MG, which decreases or avoids side effects produced by such as glucocorticosteroid or cytotoxicity. Its scope of influence and effects has been increasingly received recognition. But we still know little about its specific mechanism. The studies, which have been done earlier in our research group, showed that TWP could increase muscle contraction by promoting the transmission at neuromusclar junction. However, there is no report reported about TWP’s influence on capability of muscle contraction and also still lack of objective parameter about TWP’s effect on MG. So this experiment aims at studying the effects and mechanism of TWP on capability of muscle contraction and compound muscle action potential, so as to understand TWP’s influence and mechanism on muscle contraction more and establish a method and a kind of objective evidence for clinical treament on MG.This study consists of two parts:Part I : Effects of TWP on capability of muscle contraction of isolated gastrocnemius muscle preparation of toad were observed and recorded by using equilength transfering energy equipment.The results and conclusion are as follows:1. TWP not noly can stimulate the trasmission at neurornusclar junction, but also can enhance the inner ability of muscle contraction.2. Solvent DMSO can restrain muscle contraction.Part II: Experimental autoimmune myasthenia gravis (EAMG) was establited by injecting anitigen of AchR extracted from the muscle of calf; Influence of TWP on compound muscle action potential of gastrocnemius muscle and pronator teres muscle were observed and recorded by using neuroelectrophysiological method in established EAMG.The results and conclusion are as follows:1. EAMG was established successfully.2. TWP can increase the amplitude of compound muscle action potential of gastrocnemius muscle and pronator teres muscle.3. The effect of TWP on compound muscle action potential in different muscle has no different.4. TWP can enhence compound muscle action potential possibly not only by promoting transmission at neurornusclar junction but also by other mechanisms.5. Examining electromyography in more than one nerve-muscle groupcan increase diagnosis rate of MG.更多还原