免疫清零驯化治疗免疫性肌炎的动物模型  

Immune-ablative and tolerance inducing therapy for animal models of polymyositis

作　　者：邹纬[1] 吴学东[1] 冯晓勤[1] 裴夫瑜[1] 李娜[1] 石磊[1] 李春富[1] 

机构地区：[1]南方医科大学附属南方医院儿科,广东省广州市510515

出　　处：《中国组织工程研究与临床康复》2009年第53期10452-10456,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:根据现有理论及治疗经验,创新性提出自身免疫性疾病时体内细胞变异是永久存在的,且这些变异体细胞是引起自身免疫性疾病的原因或者同时伴有免疫细胞的变异,使用免疫清零耐受诱导新生的免疫系统对变异体细胞产生耐受,即能治愈除干细胞病变以外自身免疫性疾病的假设。目的:拟验证免疫清零驯化治疗免疫性肌炎动物模型的疗效。设计、时间及地点:随机分组、对比观察动物实验,于2008-12/2009-04在南方医院动物实验中心完成。材料:雌性成年新西兰兔1只,体质量4.1kg;雌性清洁级英格兰短毛豚鼠36只,体质量400～500g。方法:用新西兰兔肌肉匀浆混合完全弗氏佐剂对豚鼠进行免疫注射制作免疫性肌炎豚鼠模型。造模后,28只豚鼠抽签法随机分为:超大剂量清零驯化组,白消安1mg/kg,12h/次,8次,白消安给药结束后腹腔注射环磷酰胺40mg/kg,1次/d,4次,环磷酰胺给药结束后腹腔注射环孢素A3mg/kg,1次/d,持续至动物死亡;环磷酰胺组,腹腔注射环磷酰胺10mg/kg,1次/d,3次;免疫清零驯化组,白消安0.8mg/kg,环磷酰胺30mg/kg,环孢素A3mg/kg,给药次数及方式同超大剂量清零驯化组;对照组为空白对照。主要观察指标:给药前后进行全血细胞检查及生化检测,记录动物给药后生存时间,观察各组肌肉组织病理变化。结果:与对照组比较,其他组免疫后白细胞均明显降低,给药后造血功能逐渐恢复,免疫清零驯化组白细胞计数增高最明显,横纹肌病理检查发现肌肉组织病理改变以骨骼肌多发性炎症为特点。给药后超大剂量免疫清零驯化组及免疫清零驯化组谷草转氨酶、肌酸激酶较给药前明显下降(P<0.05,P<0.01),但横纹肌病理检查未见明显改变;环磷酰胺组与对照组谷草转氨酶、肌酸激酶、乳酸脱氢酶均无明显变化。超大剂量清零驯化组动物生存时间最短,环磷酰胺组与对照组无差异,免疫清零驯BACKGROUND：According to present theories and our clinical experience,immune ablative and tolerance inducing theory is proposed.Immune ablative means to clear out mutate cell clones and without transfusion of hemopoietic stem cells afterwards;intolerance inducing means to induce animal models not to react to mutate somatic cells,which avoids relapse or new occurrence of autoimmune disease.OBJECTIVE：To explore the effects of immune-ablative and tolerance inducing therapy in treating animal model of immune polymyositis （PM）.DESIGN,TIME AND SETTING：Randomized,controlled animal experiment was performed at the Animal Experimental Center of Nanfang Hospital from December 2008 to April 2009.MATERIALS：One New Zealand rabbit,female,weighing 4.1 kg and 36 England guinea pigs,female,weighing 400-500 g,were used.METHODS：New Zealand rabbit＇s muscle tissue homogenate and complete Freund＇s adjuvant （CFA） were injected into guinea pigs to make PM animal models.The 28 animal models were randomly divided into intense immune-ablative and tolerance inducing group （Busulfan 1 mg/kg,every 12 hours,totally 8 doses;followed by CTX 40 mg/kg per day for 4 days;then cyclosporine A （CsA） 3 mg/kg per day was given till animals were dead）;cyclophosphamide （CTX） group：CTX was given,10 mg/kg per day for 3days;immune-ablative and tolerance inducing group：Busulfan 0.8 mg/kg,CTX 30 mg/kg,CsA 3 mg/kg;the administration time and dose were the same as group 1.Control group was not treated.MAIN OUTCOME MEASURES：Full blood count （FBC） and biochemical index were tested before and after treatment,and surviving time was recorded.In addition,muscle pathological changes were observed.RESULTS：Compared with control group,number of white cells was significantly decreased in the other groups,and hematopoiesis function gradually restored after administration.The number of white cells in the immune-ablative and tolerance inducing group was the most,and striated muscle pathology showed PM.Following administration,the gl

关 键 词：自身免疫性疾病 多发性肌炎 免疫清零 诱导耐受 

分 类 号：R318[医药卫生—生物医学工程]