通痹灵总生物碱抑制关节破坏的细胞免疫作用机制  

Paharmacological mechanisms of cellular immunity of overall alkali of tongbiling for the treatment of joint destruction

作　　者：陈光星[1] 童娟[1] 刘清平[1] 沈晓燕[1] 赵诗哲[1] 曾耀英[2] 陈纪藩[1] 

机构地区：[1]广州中医药大学第一附属医院六内科风湿专科,广东广州510405 [2]暨南大学生命科学院组织移植与免疫中心,广东广州510632

出　　处：《细胞与分子免疫学杂志》2007年第6期527-530,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金重点项目资助(39930230);广东省重点攻关项目(2003-2005年);广东省中医药管理局课题资助(102019)

摘　　要：目的:证实通痹灵总生物碱抑制胶原诱导型关节炎(CIA)大鼠关节炎症和关节破坏的药效,揭示其调节细胞免疫的作用机制。方法:牛II型胶原混合弗氏不完全佐剂于SPF级Wistar大鼠尾根部注射,足肿后随机分为造模加生理盐水组,甲氨蝶呤(MTX)治疗组和通痹灵总生物碱(以马钱子碱和士的宁为主的生物碱,TBL总碱)治疗组,容积法评价后肢肿胀度;给药后35d,乳腺钼靶机大鼠全身摄片,计分法评价各组大鼠X光片四肢96块骨侵蚀和100个关节间隙变化;处死动物,取左前肢和右后肢近端第3足趾关节苏木素-伊红(HE)染色,评价中性粒、淋巴细胞、浆细胞浸润、滑膜细胞增生的情况;MTT法检测TBL总碱对Jurkat细胞增殖的影响;Western blot检测TBL总碱对Jurkat细胞ERK1/2磷酸化的影响。结果:造模成功后,MTX和TBL总碱给药35d都可明显抑制大鼠关节肿胀和关节破坏,与造模加生理盐水组有统计学差异(P<0.01);TBL总碱可明显抑制CIA淋巴细胞、浆细胞的浸润和滑膜增生(P<0.05),MTX可抑制滑膜增生。TBL总碱可显著抑制T细胞增殖以及ERK1/2的磷酸化。结论:TBL总碱具有抑制关节免疫炎症和关节破坏的作用,其机制可能是通过干预T细胞MAPK信号转导,抑制T细胞的活化和增殖来实现的,为TBL总碱治疗RA提供了实验依据。AIM： To investigate the effect of the overall alkali of Traditional Chinese Medicine tongbiling（TBL） which comprises brucine and strychnine alkaloids on collagen induced-arthritis （CIA） and study its paharmacological mechanisms of cellular immunity. METHODS： Bovine CII was emulsified in Freund＇s incomplete adjuvant. Wistar rats were injected with Type Ⅱ collagen intradermally at the base of the tail. After swelling, CIA groups were, randomly divided into physiological saline group and treatment group. Then the swelling of the rats＇ hindlimbs was evaluated. The whole body of the rats treated on 35 th days was photographed by mammography X-Ray. 96 joints in erosion scoring system and 100 joints in joint spacing narrow （JSN） scoring system were used to observe the joint destruction of CIA from X-Ray comprehensively and objectively. After the rats were killed, the third proximal claw pad of the right hindlimb and left forelimb were stained by HE dying, Neutrophil, lymphocyte, plasmacyte infiltration and hyperplasia of synoviocytes were assessed. Then MTT and Western blot were used to determine the effect of the overall alkali of TBL on proliferation of Jurkat cells and ERK1/2 phosphorylation of Jurkat cells, respectively. RESULTS： Inflammation of CIA joints was aggravated quickly. The swelling of CIA rats treated by MTX and overall alkali of TBL for 35 days was relieved （ P 〈 0. 05 ）. MTX and overall alkali of TBL inhibited the hyperplasia of synoviocytes. Overall alkali of TBL inhibited the infiltration of lymphocyteS and plasmacytes. Overall alkali of TBL inhibited the proliferation and ERK1/2 phosphorylation of Jurkat cells. CONCLUSION： Overall alkali of TBL could relieve joint inflammation and destruction of CIA rats by blocking the MAPK cell signalling pathway to inhibit the activation and proliferation of T cells. Our study might provide an experimental basis for treatment of rheumatoid arthritis with overall alkali of TBL.

关 键 词：胶原诱导型关节炎 关节破坏 通痹灵总碱 T淋巴细胞 细胞信号转导 

分 类 号：R392.12[医药卫生—免疫学]