【作者】 郭琳；

【导师】 李跃华； 季晓辉；

【作者基本信息】 南京医科大学 ， 病理学与病理生理学， 2004， 硕士

【摘要】 多发性硬化(multiple sclerosis，MS)是一种常见的以中枢神经系统脱髓鞘为主要特征的自身免疫性疾病，目前尚无有效的根治方法。临床上主要采用糖皮质激素等免疫抑制剂和其他非特异性抗炎疗法。近年来亦试用INF-β治疗复发-缓解型MS，但其临床疗效尚需进一步评价，且有一定的副作用。盐酸青藤碱是一种疗效确实、副反应少、新型的免疫抑制剂，已成功地被用于治疗类风湿关节炎。由于MS和类风湿关节炎具有相似免疫病理，我们推测盐酸青藤碱也许能对MS产生良好的治疗作用。因此，本研究旨在探讨盐酸青藤碱对MS的治疗作用。我们首先成功诱导了多发性硬化动物模型—实验自身免疫性脑脊髓大鼠(experimental autoimmuneencephalomyelitis，EAE)；然后给予三种不同剂量[50mg／(kg.d)、100mg／(kg.d)、150mg／(kg.d)]的青藤碱，并以甲氨蝶呤作为对照治疗药物，观察青藤碱对EAE大鼠发病时间、临床评分和病理组织的影响及血浆细胞因子TNF-α、IFN-γ、IL-10的变化。结果显示，青藤碱降低EAE动物的临床评分、减少脑和脊髓的病灶数目，降低血清TNF-α、IFN-γ水 南京医科大学硕士论文平，但对血清IL一10水平无明显影响。在此基础上我们进一步发现，青藤碱还可以抑制EAE大鼠大脑内核因子一K B(NF一KB)的活性，其抑制作用可能部分归结于促进皮质醇分泌及抑制泌乳素分泌，提示，青藤碱可能通过抑制NF一KB的活性而抑制EAE病理过程。本研究结果初步表明，青藤碱可能作为一个疗效确切、不良反应少的新型免疫抑制药用于MS的治疗。更多还原

【Abstract】 To investigate the therapeutic efficacy and mechanism of Sinomenine on experimental autoimmune encephalomyelitis (EAE) in rats, we induced the model of EAE, using female Wistar rats immunized with brain and spinal cord extracts together with complete Freund’s adjuvant, and administered Sinomenine in three different doses into the EAE rats. The severity of the disease was scored on a scale 0-6 according to the signs and symptoms. Histological examinations were performed in brain and spinal cord sections. The levels of plama TNF-, IFN-y and IL-10 were examined by ELISA. We found that Sinomenine treatment at three different doses significantly protected the rats against disease. The protection by Sinomenine was associated with significant reduction in the number of inflammatory staining in the brain and spinal cord as examined by histology. The levels of serum TNF-a, and IFN-y were markedly reduced in Sinomenine treated rats. The further experiment showed that Sinomeneine also inhibited the activity of brain NF- B, increased the level of plama cortisol, and decreased that of plama prolactin. Thus, we concluded that the protective anti-inflammatory effect of Sinomenine may be a potential candidate for use in treating patients with MS and the protection ofSinomenine may be due to the inhibition of brain NF-KB activity.更多还原