全反式维甲酸对实验性自身免疫性重症肌无力的治疗效果  

The therapeutic effect and the relative mechanisms of all-trans retinoic acid on experimental autoimmune myasthenia gravis

作　　者：李芳华 谢晓丽[2] 刘静[2] 么秀华[2] 马雪菲[2] 王丹丹[2] 王广友[2] 李呼伦[2] 

机构地区：[1]大庆市龙南医院康复中心,163001 [2]哈尔滨医科大学,150081

出　　处：《国际免疫学杂志》2013年第1期49-53,共5页International Journal of Immunology

基　　金：国家青年科学基金项目（81000536）;中国博士后科学基金（20100471094）

摘　　要：目的通过体内实验探讨全反式维甲酸（ATRA）对实验性自身免疫性重症肌无力（EAMG）的治疗效果并观察其组织病理学的改变。方法以大鼠来源的AChRα97—116多肽片段、弗式不完全佐剂、结核菌素的混合乳剂，尾根部免疫健康雌性Lewis大鼠建立EAMG实验动物模型，同时设置完全式佐剂（CFA）对照组、EAMG模型组、ATRA治疗组，其中ATRA治疗组从第一次免疫当天开始腹腔注射ATRA。依据Lennon评分法及体重监测对模型的建立及ATRA的治疗情况予以评定。于晚期发病时相（56d左右）将动物处死取材，分别取大鼠脾脏和肌肉作石蜡切片，HE染色观察各组动物脾脏和肌肉的组织病理学变化，探讨ATRA治疗EAMG的可行性。结果①成功建立EAMG动物模型。②免疫第40天后，ATRA治疗组和EAMG模型组相比较，临床症状及体重差异均有统计学意义，P临床评分=0．024，P体自=0．001。③与CFA组相比，EAMG模型组动物脾脏小梁静脉壁的厚度增大（P=0．0008），小梁静脉中的淋巴细胞数目增多（P=0．036），脾脏髓质中动脉周围淋巴鞘增宽（P=0．047），脾脏生发中心界限不清，肌纤维直径缩短（P=0．001）。④与EAMG模型组比较，ATRA治疗组动物脾小梁静脉壁的厚度较窄（P=0．043），脾髓质中动脉周围淋巴鞘变窄（P=0．012），脾脏生发中心界限相对较清晰，肌纤维直径较长（P=0．047）。结论ATRA能够缓解EAMG的临床症状，逆转EAMG的组织病理学改变。Objective To study the therapeutic effects and relative mechanisms of all-trans retinoic acid （ATRA） on experimental autoimmune myasthenia gravis （EAMG） through the view of histopathology in vivo. Methods Establishing rat EAMG models with the mixed emulsion containing AChRo97-116 peptide, ATRA-treated group, and the later was intraperitoneally injected with ATRA from the first day of immunization. The clinical scores and body weight were evaluated. In the late onset phase （56 days）, animals were killed and their spleen and muscle were prepared for paraffin sections. HE staining was performed to observe the his- topathological changes to explore the feasibility of ATRA treatment on EAMG. Results EAMG animal model was successfully established. After 40 days of immunization, the clinical scores and weight between EAMG and ATRA-treated group were significantly different, Pclinical = 0. 024, Pboay weith, = 0. 001 ; Compared with the CFA group, EAMG model group＇ s splenic trabecular vein wall thickness was increased （ P = 0. 000 8 ） , lymphocytes in the trabecular vein were increased （ P = 0. 036） , splenic periarterial lymphatic sheathes were widened （ P = 0. 047 ） , the circumscription of splenic germinal centers were unclear, and the myofibril diameter became short （ P = 0. 0 0 1 ） ; Compared with the EAMG model group , ATRA - treated group animals ＇ splenic trabecular vein wall thickness narrow （ P = 0. 043 ）, splenic periarterial lymphatic sheathes became narrow （P =0.012）, the splenic germinal centers are better-defined boundaries, and the myofibril diameter became long （P = 0.047）. Conclusion ATRA could alleviate the clinical symptoms of EAMG, reverse these patho- logical changes of EAMG.

关 键 词：全反式维甲酸 实验性自身免疫性重症肌无力 乙酰胆碱受体 HE染色 

分 类 号：R74[医药卫生—神经病学与精神病学]