载脂蛋白E对实验性自身免疫性脑脊髓炎星形胶质细胞的影响

发布时间：2018-01-19 08:03

本文关键词： 实验性自身免疫性脑脊髓炎载脂蛋白E 水通道蛋白4 胶质纤维酸性蛋白　出处：《广西医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的研究载脂蛋白E (ApoE)对实验性自身免疫性脑脊髓炎(EAE)模型小鼠病灶中的星形胶质细胞的影响。方法采用髓鞘少突胶质细胞糖蛋白多肽35-55 (MOG35-55)作为抗原,分别诱导敲除ApoE基因的C57BL/6小鼠(ApoE-/-)及野生型(WT)C57BL/6J小鼠,建立EAE模型,对应设立E-ApoE-/-组和E-WT组。将野生型C57BL/6J小鼠注射等量生理盐水以代替MOG35-55,设立正常对照组(C-WT)。免疫后第0-35天,每天上午由同一人对小鼠进行神经功能缺损评分,并同时记录。免疫后第35天,取各组小鼠的大脑和脊髓做石蜡切片,行HE染色,观察各组小鼠脑组织中炎性细胞的浸润情况。免疫组织化学染色法检测各组小鼠的大脑和脊髓中水通道蛋白4(AQP4)与胶质纤维酸性蛋白(GFAP)的表达情况。结果E-ApoE-/-组和E-WT组于免疫后第11天相继发病,发病率达100%。C-WT组无小鼠发病,活动度正常。两组EAE小鼠的神经功能缺损症状随时间的延长而逐渐加重。与E-WT组小鼠比较,E-ApoE-/-组小鼠的神经功能缺损评分峰值显著升高(P0.05)；同时,E-ApoE-/-组小鼠的大脑和脊髓中浸润的炎性细胞显著多于E-WT组；与正常对照组小鼠相比,E-ApoE-/-组小鼠和E-WT组小鼠的大脑和脊髓中AQP4、GFAP的表达量均显著升高(P均0.05)；另外,E-ApoE-/-组小鼠的大脑和脊髓中AQP4、GFAP的表达量均显著高于E-WT组(P均0.05)。结论EAE小鼠中存在炎性浸润以及星形胶质细胞水肿和增生,而ApoE的缺乏可以加重这些病理改变,ApoE可以作为MS防治的新的切入点,为MS的防治提供新的方向和理论参考。
[Abstract]:Objective to study the apolipoprotein E (ApoE) on experimental autoimmune encephalomyelitis (EAE) effects of lesions in a mouse model of astrocytes. Methods using myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) as antigen, were induced in ApoE knockout mice (C57BL/6 ApoE-/-) and wild type (WT) C57BL/6J mice, EAE model is established, corresponding to the establishment of E-ApoE-/- group and E-WT group. The wild type C57BL/6J mice were injected with normal saline instead of MOG35-55, a normal control group (C-WT). 0-35 days after immunization, every morning by the same person on mouse nerve function deficit score was recorded at the same time, and thirty-fifth days. After immunization, the brain and spinal cord of mice were taken and paraffin sections were stained with HE, observed the infiltration of inflammatory cells in the brain tissue of mice. Immunohistochemical staining in the mice brain and spinal cord through the water Protein 4 (AQP4) and glial fibrillary acidic protein (GFAP). The expression results of E-ApoE-/- group and E-WT group on the eleventh day after immunization after onset, the incidence rate of 100%.C-WT group activity. Normal incidence of mice, prolong the neurological symptoms of EAE mice in two groups with time gradually increased. Compared with the mice in group E-WT, the neurological deficit scores significantly increased the peak in E-ApoE-/- group (P0.05); at the same time, the infiltration of inflammatory cells of the brain and spinal cord of mice in E-ApoE-/- group was significantly higher than in group E-WT; compared with normal control mice, AQP4 brain and spinal cord of mice in E-ApoE-/- group and E-WT group of mice, the expression of GFAP increased significantly (P < 0.05); in addition, AQP4 brain and spinal cord of mice in E-ApoE-/- group, the expression of GFAP was significantly higher than that of group E-WT (P < 0.05). There are inflammatory infiltration and astrocyte edema and the conclusion of EAE in mice The lack of ApoE can aggravate these pathological changes, and ApoE can be used as a new entry point for the prevention and control of MS, which provides a new direction and theoretical reference for the prevention and control of MS.

【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R744.51

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