1,25-双羟维生素d3对实验性自身免疫性脑脊髓炎小鼠自噬的调控作用

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1、授予单位代码10089学号或申请号20122075HebeiMedicalUniversity硕士学位论文科学学位1，25-双羟维生素D3对实验性自身免疫性脑脊髓炎小鼠自噬的调控作用研究生：甄超导师：郭力教授专业：神经病学二级学院：第二医院2015年3月河北医科大学学位论文使用授权及知识产权归属承诺本学位论文在导师（或指导小组）的指导下，由本人独立完成。本学位论文研究所获的研究成果，其知识产权归河北医科大学所有。河北医科大学有权对本学位论文进行交流、公开和使用。凡发表与学位论文主要内容相关的论文，第一署名单位

2、为河北医科大学，试验材料、原始数据、申报的专利等知识产权归河北医科大学所有。否则，承担相应法律责任。研究生签名：二级学院领导签章‘：>0七^才.日河北医科大学研究生学位论文独创性声明本论文是在导师指导下进行的研究工作及取得的研究成果，除了文中特别加以标注和致谢等内容外,文中不包含其他人已经发表或撰写的研究成果，指导教师对此进行了审定。本论文由本人独立撰写，文责自负。研究生签名:导师签章：年士月目录中文摘要·····················································

3、························1英文摘要·············································································4英文缩写·············································································8研究论文1，25-双羟维生素D3对实验性自身免疫性脑脊髓炎小鼠自噬的调控作用前言····························

4、·················································9材料与方法····································································10结果·············································································19附图·················································

5、····························22讨论·············································································26结论·············································································29参考文献·····························································

6、··········29综述维生素D、自噬与疾病··················································33致谢···················································································42个人简历·············································································43中文摘要1，25-双羟

7、维生素D3对实验性自身免疫性脑脊髓炎小鼠自噬的调控作用摘要目的：多发性硬化不仅是中枢神经系统的自身免疫性疾病，也是一种神经变性疾病，其发病率和地理纬度具有明显相关性，越远离赤道，多发性硬化的发病率越高。本实验选用1,25(OH)2D3作为干预药物，研究其治疗多发性硬化的有效性，不仅研究其对中枢神经系统白质髓鞘的影响，还深入研究对灰质神经元的作用，并进一步探索其潜在的作用机制。方法：将27只周龄在8-10周左右，体重在18-20g左右的C57BL/6雌性小鼠随机分为正常对照组，EAE组，VD3组（即1,25(O

8、H)2D3给药组）,各组均为9只。以MOG多肽为抗原免疫后两组小鼠建立EAE动物模型。以250μg人工合成MOG35-55多肽溶到500μl生理盐水中，和等体积含1mg/ml结核菌素的完全福氏佐剂(CFA)混合，加入结核杆菌H37Ra使结核菌素补充至400ng，充分混匀至油包水乳剂，制成完全抗原，双侧背部分4点皮下注射。于免疫后的第0和48h两次给予小鼠腹腔内注射500ng的百日咳毒素，以建立小鼠的