小剂量阿托伐他汀对实验性自身免疫性重症肌无力大鼠的治疗作用

山东大学学报(医学版) ›› 2012, Vol. 50 ›› Issue (7): 26-31.

小剂量阿托伐他汀对实验性自身免疫性重症肌无力大鼠的治疗作用

刘莹1，李晓丽1，徐华2，王杉1，张民1，李亨1，段瑞生1

1.山东大学附属千佛山医院神经内科，济南 250014； 2.泰安市中心医院康复科，山东泰安 271000

收稿日期:2012-02-24 出版日期:2012-07-10 发布日期:2012-07-10
通讯作者: 段瑞生(1964- )，男，教授，博士生导师，主要从事神经免疫的研究。 E-mail:ruisheng-duan@yahoo.com
作者简介:刘莹(1982- )，女，硕士研究生，主要从事重症肌无力的研究。 E-mail:liuyinghelen.student@sina.com
基金资助:
山东省医药卫生科研基金 (2007HZ079)；国家自然科学基金(30771989和81171128)；教育部留学回国人员科研启动基金［教外司留(2008)890号］。

Effects of lower dose of atorvastatin on experimental autoimmune myasthenia gravis inrats

LIU Ying1, LI Xiao-li1, XU Hua2, WANG Shan1, ZHANG Min1, LI Heng1, DUAN Rui-sheng1

1． Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China;
2. Department of Rehabilitation Medicine, The Central Hospital of Affilliated to Taian, Taian 271000, China

Received:2012-02-24 Online:2012-07-10 Published:2012-07-10

摘要/Abstract

摘要：

目的探究阿托伐他汀对实验性自身免疫性重症肌无力(EAMG)大鼠的免疫调节机制。方法用人工合成的大鼠乙酰胆碱受体α亚基97-116肽段免疫Lewis大鼠制造重症肌无力(MG)模型，随机分为阿托伐他汀治疗组和对照组，采用Lennon评分标准评价大鼠病情, 采用双盲法隔天评估大鼠肌力并记录体质量；免疫组化检测大鼠胸腺抑制性转录调节因子Foxp3的表达，以此反映调节性T细胞(Treg)的数量；CCK-8检测淋巴结单个核细胞增殖；ELISA检测细胞培养上清液IL-4及血清抗R97-116抗体的水平。结果阿托伐他汀治疗组大鼠临床症状较对照组明显缓解，胸腺Foxp3的表达及细胞培养上清液IL-4的水平均高于对照组，血清抗R97-116抗体水平低于对照组。结论阿托伐他汀通过上调Treg和Th2型细胞因子IL-4的水平，从而降低血清中抗R97-116抗体水平，缓解EAMG病情。

关键词: 他汀类药物；重症肌无力，实验性自身免疫性；T淋巴细胞；白细胞介素4；大鼠

Abstract:

Objective To investigate the immunological mechanism of atorvastatin in experimental autoimmune myasthenia gravis (EAMG) in rats. Methods Atorvastatin was administered intraperitoneally to the EAMG rats. The intrathymic expression of fork head box protein 3 (Foxp3) was analyzed by the immunohistochemistry and the lymphocyte proliferation was determined by CCK-8. The level of IL-4 in culture supernatants of lymph node mononuclear cells (MNC) and antiR97-116 IgG in the serum were detected by ELISA. Results Administration of atorvastatin ameliorated clinical signs of EAMG, increased the number of the Foxp3-positive cells in the thymic medulla, up regulated the level of IL-4 in culture supernatants, and decreased the level of serum anti-R97-116 IgG. Conclusion Lower dose of atorvastatin could ameliorate EAMG by up-regulation of Treg and Th2 cytokines.

Key words: Statins; Myasthenia gravis, experimental autoimmune; Tlymphocytes; Interleukin4; Rats

中图分类号:

R746.1

刘莹1，李晓丽1，徐华2，王杉1，张民1，李亨1，段瑞生1. 小剂量阿托伐他汀对实验性自身免疫性重症肌无力大鼠的治疗作用[J]. 山东大学学报(医学版), 2012, 50(7): 26-31.

LIU Ying1, LI Xiao-li1, XU Hua2, WANG Shan1, ZHANG Min1, LI Heng1, DUAN Rui-sheng1. Effects of lower dose of atorvastatin on experimental autoimmune myasthenia gravis inrats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(7): 26-31.

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