雪旺氏细胞凋亡在TNFRⅠ -/-鼠实验性自身免疫性神经炎发病机制中的作用  

Role of Schwann cells apoptosis in pathogenesis of EAN in TNFRⅠ knock out mice

作　　者：金涛[1] 祝捷[1] 

机构地区：[1]吉林大学第一医院神经内科,吉林长春130021

出　　处：《吉林大学学报（医学版）》2007年第2期279-282,共4页Journal of Jilin University：Medicine Edition

基　　金：瑞典国家基金资助课题(K2004-33X-13133-06A)

摘　　要：目的:建立实验性自身免疫性神经炎(EAN)在肿瘤坏死因子α受体I(TNFRⅠ)基因敲除鼠(TNFRⅠ-/-)的动物模型,进一步研究雪旺氏细胞凋亡在其发病机制中的作用。方法:采用周围神经P0蛋白180-199肽段皮下免疫方法分别在TNFRⅠ-/-及野生鼠C57BL/6上制备EAN动物模型;连续观察EAN的发病过程、疾病严重程度并进行临床症状评分;免疫后第22天取2组动物雪旺氏细胞进行原代培养,通过流式细胞仪检测Fas及Annexin-Ⅴ(Annexin-Ⅴ+/PI-)在雪旺氏细胞的表达。结果:TNFRⅠ-/-组EAN症状高峰临床评分(1.50±0.19)较野生型组(1.90±0.16)明显减低;TNFRⅠ-/-EAN组雪旺氏细胞Fas阳性表达率为(88.03±1.40)%,野生型组为(94.70±1.53)%,两组比较差异有显著性(P<0.05);Annexin-Ⅴ(Annexin-Ⅴ+/PI-)在TNFRⅠ-/-组雪旺氏细胞的阳性表达率为(8.78±0.94)%,野生型组为(13.03±4.15)%,TNFRⅠ-/-组呈降低趋势,但两组比较差异无显著性(P>0.05)。结论:TNFRⅠ可能通过增加雪旺氏细胞的凋亡进而引起周围神经损伤而加重EAN的临床症状。Objective To study the role of Schwann cells apoptosis in the pathogenesis of experimental autoimmune neuritis （EAN） in TNF receptor Ⅰ knock out （TNFR 1-/-） mice. Methods For induction of EAN, TNFRI-/- and wild type C57BL/6 mice were immunized by subcutaneous injection into the back with the peripheral nerve P0 protein peptide 180-199; clinical scores of EAN were assessed and scored immediately before immunization （day 0） and thereafter every other day until day 46 post immunization （p. i. ）. On day 22 p. i. , Schwann cells were collected from the two groups and cultivated in vitro. The expressions of Fas and Annexin-V （Annexin-Ⅴ ＋/PI-） on Schwann cells from TNFR Ⅰ-/- and wild type EAN were detected by flow cytometry. Results More light clinical signs of EAN were observed in the TNFR [ -/- mice （1.50：k0. 19） than in wild type mice （1.90 ± 0.16 ）; the percentage of Fas expression on Schwann cells was significantly decreased in TNFRⅠ -/- mice （88.03%±1. 40%）ascompared with wild type mice （94.70%＋1.53%） （P〈0.05）. An decreased tendency of Annexin-Ⅴ （Annexin-Ⅴ ＋/PI-） expression on Schwann cells was seen in TNFR Ⅰ -/- mice （8.78%±0.94%） as compared with wild type mice （13. 03%±4.15%）, but no significant difference. Conclusion TNFR Ⅰ may induce peripheral nerve injury and aggravate EAN through increasing Schwann cells apoptosis.

关 键 词：神经炎 实验变应性 受体 肿瘤坏死因子 小鼠 基因敲除 雪旺氏细胞 抗原 CD95 钙磷脂 结合蛋白V 

分 类 号：R745.4[医药卫生—神经病学与精神病学]