青藤碱对胶原诱导型关节大鼠滑膜细胞增殖及凋亡影响的研究  

Study of sinomenine on synoviocytes hyperplasia and apoptosis in collagen induced arthritis rat

作　　者：陈光星[1] 刘良[2] 赵诗哲[1] 刘清平[1] 童娟[1] 简任佑[1] 曾耀英[3] 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,510405 [2]香港浸会大学中医药学院 [3]暨南大学生命科学院组织移植与免疫中心

出　　处：《中华风湿病学杂志》2005年第5期284-287,共4页Chinese Journal of Rheumatology

基　　金：国家自然科学基金重点资助项目(39930230);广东省中医药管理局课题资助项目(102019)

摘　　要：目的研究青藤碱对胶原诱导型关节炎(CIA)大鼠关节炎症,滑膜增生、凋亡及突变型p53的影响,揭示青藤碱抗类风湿关节炎(RA)可能的作用途径。方法采用牛Ⅱ型胶原混合弗氏不完全佐剂于W istar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(M TX)治疗组和青藤碱(SIN O)治疗组,采用容积法和计分法分别评价后肢肿胀度和四肢关节炎症程度;左前肢和右后肢近端第3足趾关节苏木素-伊红(H E)染色,评价中性粒细胞、淋巴细胞、浆细胞浸润、滑膜细胞增生和纤维组织增生的情况;对足肿胀和病理各项指标进行回归性分析。碱性磷酸酶标记法检测大鼠滑膜细胞凋亡;免疫组织化学法检测突变型p53的表达。比较M TX和SINO灌胃治疗后各项指标的差异。结果CIA大鼠造模后,炎症迅速发展,1周内即可达到肿胀高峰,然后逐渐消退,在第21～25天后又出现第2个炎症高峰。药物治疗17d后抑制CIA肢炎症的作用逐渐显现出来。M TX和SIN O都可明显抑制第2个炎症高峰,后肢肿胀度和四肢肿胀积分在35d与造模加生理盐水组差异有统计学意义(P<0.01);病理结果中,CIA大鼠关节表现为单个核炎症细胞浸润(包括中性粒细胞、淋巴细胞和浆细胞的浸润),滑膜细胞增生、纤维组织增生;足肿与淋巴细胞浸润,滑膜增生呈直线回归关系,其中以滑膜增生为主(P<0.Objective To investigate sinomenine (SINO) on the treatment of limbs inflammation, synovium hyperplasia and apoptosis in collagen induced arthritis rat (CIA) and to explore its pharmacological mechanism on treatment of rheumatoid arthritis. Methods Bovine CⅡ was emulsified in Freund′s incomplete adjuvant. Wistar rats were injected intradermally at the base of the tail. After joint swollen were developed, CIA groups were then randomly divided into physiological saline group and treatment groups. The swelling of hindlimb and inflammation of four limbs of CIA rat were evaluated, using Cubic method and clinical score respectively. The third proximal foot pad of right hindlimb and left forelimb were stained by HE dying, whilst neutrophil, lymphocyte and plasmacyte infiltration, hyperplasia of fibrous, and hyperplasia of fibrous tissue were assessed. Apoptosis of synoviocytes were detected with phosphatase marked method. The rates of p53 mutations expression were examined by immuno-histochemistry method. Effect of methotrexate (MTX) and sinomenine (SINO) on CIA were observed. Result Inflammation of CIA joint were aggravated quikly. Swelling reached the peak in one week, and then relieved gradually. Swelling reached the second peak from 21 days to 25 days. MTX and SINO could inhibit the second peak of inflammation of CIA rats after treated for 17 days. At day 35, MTX and SINO could relieve swelling of hindlimbs and decrease scores of limbs of CIA (P<0.05). There were infiltration of neutrophils, lymphocytes and plasmacytes, hyperplasia of synoviocytes, hyperplasia of fibrous tissue, and cartilage destruction in pathology. MTX and SINO could inhibit hyperplasia of synoviocytes. SINO could inhibit infiltration of plasmacytes. The number of syvoviocytes apoptosis was increased. MTX and SINO could increase the number of synoviocytes apoptosis as well as inhibit p53 mutation expression (P<0.05). Conclusion SINO may down regulates p53 mutation expression and inhibit hyperplasia of synoviocytes and induce apoptosis of syno

关 键 词：滑膜细胞增殖 青藤碱 影响的研究 突变型p53 滑膜细胞增生 滑膜细胞凋亡 CIA大鼠 胶原诱导型关节炎 纤维组织增生 抗类风湿关节炎 弗氏不完全佐剂 免疫组织化学法 生理盐水组 中性粒细胞 滑膜增生 Wistar 苏木素-伊红 炎症细胞浸润 

分 类 号：R285[医药卫生—中药学]