实验性肌炎动物模型制作的研究  

Experimental autoimmune myositis in rat

作　　者：谢瑶[1] 卢昕[1] 王国春[1] 王泰龄[2] 李鸿[3] 郭建[3] 

机构地区：[1]北京中日友好医院风湿免疫科,100029 [2]北京中日友好医院病理科,100029 [3]北京中日友好医院临床医学研究所动物室,100029

出　　处：《中华风湿病学杂志》2007年第11期662-665,706,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金(30170885);北京中日友好医院2005年重点学科基金

摘　　要：目的建立实验性肌炎动物模型,研究特发性炎性肌病的发病机制。方法将50只健康的雄性SD大鼠随机分成两组:模型组40只,对照组10只。兔骨骼肌制备肌匀浆。模型组用肌匀浆与弗氏完全佐剂完全乳化后皮下免疫注射1ml,对照组用生理盐水替代肌匀浆,每周免疫1次,连续免疫5次。前2周同时腹腔注射百日咳毒素1ml。分别于免疫注射后各周取大鼠的骨骼肌组织,观察其肌活检病理、免疫组织化学的改变,同时检测血清肌酶水平,并与人类炎性肌病比较。结果模型组肌酶升高与对照组间有显著差别。病理改变以骨骼肌多发性炎症为特点:横纹肌呈灶性分布的肌纤维变性、坏死,横纹消失;周围炎性细胞浸润;肌纤维粗细不等、染色不一。病理分级以2a级为主。单个核细胞浸润以CD8^+ T细胞为主,主要定位于肌内膜。骨骼肌细胞膜上主要组织相容性复合体(MHC)-Ⅰ类分子表达增加。结论用异种动物骨骼肌匀浆免疫大鼠可诱导出炎性肌病动物模犁,与人类炎性肌病在临床表现、组织病理和免疫组织化学方面有相似之处。Objective The aim of our study is to establish and characterize the animal model for autoimmune myositis, Methods Fifty male SD rats were randomly divided into 2 groups： model group （n=40） and control group （n=10）, The model group rats were immunized with muscle homogenate every week for 5 weeks and received an injection of 2 μg pertussis toxin at the first and second week. As controls, 10 SD rats were injected with an equal volume of normal saline, Tissue specimens from limb skeletal muscles were obtained at 1, 2, 3, 4, 5 weeks after injection. At the same time, the blood samples were collected, and the level of CPK was measured. Results The model group had significantly elevated serum CPK levels. There were multiple inflammatory lesions in the skeletal muscles, Local degeneration and necrosis of muscle fibers with disappeared transverse striation, mononuclear cell infiltration in the interstitial could be observed. The pathologic grade was mainly 2a. The infiltrating mononuclear cells were predominantly CD8^＋T cells that mainly located in the endomysium. MHC class Ⅰ antigen expression on muscle fiber membranes in the model group was upregulated, Conclusion The experimental autoimmune myositis induced by syngeneic skeletal muscle homogenate in SD rat is pathologically similar to human myositis. It can be used as a good model for human myositis and provides the basis for the etiopathology and therapeutical studies.

关 键 词：大鼠 动物模型 肌炎 

分 类 号：R593.2[医药卫生—内科学] R-332[医药卫生—临床医学]