雷公藤多甙对佐剂性关节炎模型大鼠踝关节相关指标的影响
뢰공등다대대좌제성관절염모형대서과관절상관지표적영향
Effects of polyglycosides of tripterygium wilfordii hook F on the relative data of ankle joints of model rats with adjuvant arthritis
  • 万方数据
    中国临床康复 중국림상강복
    CHINESE JOURNAL OF CLINICAL REHABILITATION
    2006年 47期 189-192 ,共4页

    杨琴%杨桂枝%王蕾%马玉琼%田汉文

    양금%양계지%왕뢰%마옥경%전한문

    关节炎%滑膜%雷公藤%模型,动物%踝关节 關節炎%滑膜%雷公籐%模型,動物%踝關節
    관절염%활막%뢰공등%모형,동물%과관절
    背景:类风湿性关节炎是常见的自身免疫性疾病.近年来雷公藤多甙广泛应用于类风湿性关节炎治疗,其治疗过程中对关节滑膜炎症的影响及对类风湿性关节炎的预防作用有待研究.目的:观察雷公藤多甙对佐剂性关节炎模型大鼠踝关节相关指标的影响.设计:随机对照动物实验.单位:四川大学基础医学与法医学院组织胚胎学与神经生物学教研室.材料:选用20只健康清洁级雌性SD大鼠,体质量(200±15)g,鼠龄二三个月,由四川大学实验动物中心提供.氟氏完全佐剂为Sigma公司产品,雷公藤多甙为湖南株州制药三厂产品(批准文号:湘卫药准字(2005)第055172号.剂量:10 mg/片).方法:实验于2004-05/2006-03在四川大学组织胚胎学和神经生物学教研室完成.抽签法随机将大鼠分为正常组、模型组、预防组及治疗组,每组5只.正常组不造模,不给药物治疗;模型组于实验开始后,分别在各个大鼠左后足垫部皮下注射氟氏完全佐剂0.2 mL,不给药物治疗;预防组造模方法同模型组,造模后第7天开始灌胃给予雷公藤多甙,用药剂量以大鼠体表面积换算公式计算,1次/d,每次30 mg/kg,共7 d;治疗组造模方法同模型组,造模后第19天开始灌胃给予雷公藤多甙,方式和疗程同预防组.①采用足跖容积法于造模前,造模后2,10,15,19,22,26 d不同时间点观察记录大鼠原发侧与继发侧关节后肢肿胀程度.②根据其余未注射的3只肢体的病变程度及指间趾间关节是否发炎,评价大鼠关节炎指数(0分:肿胀度≤5%;1分:肿胀≤15%;2分:15%＜肿胀≤30%;3分:30%＜严重肿胀≤60%;4分:肿胀＞60%),把每个关节的得分累计起来,即为每只大鼠的关节炎指数.③造模后28 d取材,将大鼠灌注固定后,取完整踝关节切片,苏木精-伊红染色后观察大鼠踝关节滑膜组织的改变.主要观察指标:各组大鼠关节肿胀程度、关节炎指数及踝关节滑膜组织学观察.结果:大鼠20只均进入结果分析.①造模2 d后,除正常组外,其他各组大鼠原发侧关节均出现明显肿胀,造模2～26 d各时间点大鼠足跖容积均大于正常组(t=2.315～3.041,P＜0.05);预防组大鼠造模后10,15,19,22,26 d原发侧足跖容积小于模型组(t=2.064～2.683,P＜0.05);治疗组大鼠造模后22,26 d原发侧足跖容积小于模型组(t=2.112～2.578,P＜0.05).造模15 d后,模型组和治疗组大鼠继发侧足跖容积均大于正常组(t=2.201～2.546,P＜0.05),预防组大鼠造模15,19,22,26 d继发侧足跖容积小于模型组(t=2.373～2.425,P＜0.05);治疗组大鼠造模26 d继发侧足跖容积小于模型组(P＜0.05).②造模14 d,模型组大鼠关节炎指数为(8.3±2.0)分,预防组为(0.4±0.95)分,预防组较模型组明显降低(t=2.64,P＜0.05);造模26天,治疗组为(7.3±1.3)分,明显低于模型组(11.2±0.9)分(t=3.26,P＜0.05).③正常组大鼠踝关节腔内干净,关节软骨表面光滑,软骨无退行性变,滑膜组织无增生.模型组大鼠原发侧踝关节滑膜增生,滑膜细胞数量增多,体积增大,排列为多层;滑膜下组织水肿,充血,炎性细胞浸润.模型组继发侧继发性病变表现为滑膜增生,踝关节滑膜下组织水肿.预防组原发侧踝关节滑膜与模型组比较,滑膜炎症反应减弱,增生程度减轻.继发侧踝关节滑膜未见明显增生.治疗组原发侧及继发侧踝关节滑膜与模型组比较,滑膜组织增生减少,炎症反应减轻.结论:雷公藤多甙能显著减轻大鼠足跖关节肿胀度,关节炎症指数,减轻踝关节滑膜病理改变,且能预防继发性病变的出现.
    배경:류풍습성관절염시상견적자신면역성질병.근년래뢰공등다대엄범응용우류풍습성관절염치료,기치료과정중대관절활막염증적영향급대류풍습성관절염적예방작용유대연구.목적:관찰뢰공등다대대좌제성관절염모형대서과관절상관지표적영향.설계:수궤대조동물실험.단위:사천대학기출의학여법의학원조직배태학여신경생물학교연실.재료:선용20지건강청길급자성SD대서,체질량(200±15)g,서령이삼개월,유사천대학실험동물중심제공.불씨완전좌제위Sigma공사산품,뢰공등다대위호남주주제약삼엄산품(비준문호:상위약준자(2005)제055172호.제량:10 mg/편).방법:실험우2004-05/2006-03재사천대학조직배태학화신경생물학교연실완성.추첨법수궤장대서분위정상조、모형조、예방조급치료조,매조5지.정상조불조모,불급약물치료;모형조우실험개시후,분별재각개대서좌후족점부피하주사불씨완전좌제0.2 mL,불급약물치료;예방조조모방법동모형조,조모후제7천개시관위급여뢰공등다대,용약제량이대서체표면적환산공식계산,1차/d,매차30 mg/kg,공7 d;치료조조모방법동모형조,조모후제19천개시관위급여뢰공등다대,방식화료정동예방조.①채용족척용적법우조모전,조모후2,10,15,19,22,26 d불동시간점관찰기록대서원발측여계발측관절후지종창정도.②근거기여미주사적3지지체적병변정도급지간지간관절시부발염,평개대서관절염지수(0분:종창도≤5%;1분:종창≤15%;2분:15%＜종창≤30%;3분:30%＜엄중종창≤60%;4분:종창＞60%),파매개관절적득분루계기래,즉위매지대서적관절염지수.③조모후28 d취재,장대서관주고정후,취완정과관절절편,소목정-이홍염색후관찰대서과관절활막조직적개변.주요관찰지표:각조대서관절종창정도、관절염지수급과관절활막조직학관찰.결과:대서20지균진입결과분석.①조모2 d후,제정상조외,기타각조대서원발측관절균출현명현종창,조모2～26 d각시간점대서족척용적균대우정상조(t=2.315～3.041,P＜0.05);예방조대서조모후10,15,19,22,26 d원발측족척용적소우모형조(t=2.064～2.683,P＜0.05);치료조대서조모후22,26 d원발측족척용적소우모형조(t=2.112～2.578,P＜0.05).조모15 d후,모형조화치료조대서계발측족척용적균대우정상조(t=2.201～2.546,P＜0.05),예방조대서조모15,19,22,26 d계발측족척용적소우모형조(t=2.373～2.425,P＜0.05);치료조대서조모26 d계발측족척용적소우모형조(P＜0.05).②조모14 d,모형조대서관절염지수위(8.3±2.0)분,예방조위(0.4±0.95)분,예방조교모형조명현강저(t=2.64,P＜0.05);조모26천,치료조위(7.3±1.3)분,명현저우모형조(11.2±0.9)분(t=3.26,P＜0.05).③정상조대서과관절강내간정,관절연골표면광활,연골무퇴행성변,활막조직무증생.모형조대서원발측과관절활막증생,활막세포수량증다,체적증대,배렬위다층;활막하조직수종,충혈,염성세포침윤.모형조계발측계발성병변표현위활막증생,과관절활막하조직수종.예방조원발측과관절활막여모형조비교,활막염증반응감약,증생정도감경.계발측과관절활막미견명현증생.치료조원발측급계발측과관절활막여모형조비교,활막조직증생감소,염증반응감경.결론:뢰공등다대능현저감경대서족척관절종창도,관절염증지수,감경과관절활막병리개변,차능예방계발성병변적출현.
    BACKGROUND: Reumatoid arthritis (RA) is a well-known autoimmune disease. Recently, polyglycosides of tripterygium wilfordii hook F (T Ⅱ), a traditional Chinese herb, has been widely used to treat rheumatoid arthritis.But the effects of TⅡ on the joints' synovium inflammation and whether TⅡcan prevent the reumatoid arthritis need to be investigated further.OBJECTIVE: To study the effects of T Ⅱ on the relative data of ankle joints of adjuvant arthritis (AA) rats.DESIGN: A randomized controlled experiment based on rats. SETTING: Departments of Histology and Embryology and Neurobiology, West China School of Preclinical and Forensic Medicine, Sichuan University. MATERIALS: A total of 20 healthy clean grade female SD rats, aged 2 to 3 months old, weighing 185-215 g, were provided by the Experimental Animal Center of West China Medical Center of Sichuan University. Fre und's complete adjuvant (FCA) was produced by Sigma Company. TⅡ was produced by Zhuzhou 3rd pharmacy of Hunan Province (certification number: 2005 No 055172, 10 mg/pill).METHODS: The experiment was completed in Department of Histology and Embryology and Neurobiology in Sichuan University from May 2004 to March 2005. ① All the 20 rats were randomly divided into 4 groups with 5 rats in each group by lots: normal group, without Freund's complete adjuvant (FCA) injection and TⅡ administration; model group, with FCA intradermal injection (0.2 mL) into the left hind paw and without TⅡ administration; TⅡ preventive group, first we use the same way as model group to replicate the AA model in rats, then on the 7th day AA rats were feed by TⅡ 30 mg/kg every day for 7 days; TⅡ therapeutic group, AA rats model were built with the same way as model group, on the 19th day AA rats were feed by TⅡ 30 mg/kg every day for 7 days. During this period, the swelling dimension of hind paw both primary and secondary are mea sured before immunization with FCA and after immunization, that was, on the 2nd, 10th, 15th, 19th, 22nd and 26th days. ② Arthritis index have been recorded according to inflammatory state of other three uninjected limbs.③ On the 28th day, all the rats were killed, the ankle joints are collected after perfusion-fixation. These joints were sectioned and colorated with H. E staining. Then we observe the histopathological changes in the synovium of ankle joints. MAIN OUTCOME MEASURES: Swelling dimension of joints and arthritis index, histopathology of anklebone joint's synovium. RESULTS: All of the 20 rats completed the experiment without missing. ① On the 2nd day after FCA injection, the primary hind paw of other three groups beside normal group appeared obvious swelling; from 2nd to 26th days, the volume of hind paw in other three groups was larger than that of normal group (t=2.315-3.041, P ＜ 0.05). The volume of primary hind paw in TⅡ preventive group at different time points (10th, 15th, 19th, 22nd and 26th days) was obviously less than that of model group (t=2.064-2.683, P ＜ 0.05). The volume of primary hind paw in TⅡ therapeutic group on the 22nd and 26th days was less than that of model group (t=2.112-2.578, P ＜ 0.05). Fifteen days after FCA injection, the volume of secondary hind paw in model group and T Ⅱ therapeutic group was larger than that of normal group (t=2.201-2.546, P ＜ 0.05). On the 15th, 19th, 22nd and 26th days, the volume of secondary hind paw in T Ⅱ preventive group was obviously less than that of model group (t=2.373-2.425, P ＜ 0.05). The volume of secondary hind paw in T Ⅱ therapeutic group on the 26th day was obviously less than model group (P ＜ 0.05). ② On the 14th day after FCA injection(after T Ⅱ preventive administration for 7 days), arthritis index of model group was (8.3±2.0) points, while arthritis index of TⅡ preventive group was (0.4±0.95) points (t=2.64, P ＜ 0.05), there was an obvious decline in T Ⅱ preventive group compared with model group. On the 26th day after FCA injection (after TⅡ therapeutic administration for 7 days), arthritis index of model group was (11.2±0.7), whileinflammatory disease in AA rats and prevent the secondary arthritis in the rats of AA as well.
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