EAE发病机制中MALT1、IL-17作用的探讨

发布时间：2018-11-02 19:33

【摘要】：目的:通过建立实验性自身免疫性脑脊髓炎(EAE)小鼠模型,观察小鼠脑组织中黏膜相关淋巴组织淋巴瘤转运蛋白1与血清白介素-17(Interleukin-17)的表达情况,并探讨两者在EAE发病机制中的作用。进一步探究MALTI是否可以作为多发性硬化(MS)的治疗靶点,以便寻找治疗MS的新手段。方法:将36只C57BL/6雌性小鼠按照随机数字表法分为EAE组和佐剂组各18只,EAE组采用MOG与完全弗氏佐剂的沫状混合物制备EAE模型,佐剂组仅给予弗氏佐剂。观察每只实验动物发病情况并每隔2 d进行一次神经功能评分。分别于免疫后14 d、24 d、40 d两组小鼠随机各取6只,心脏取血并4%多聚甲醛灌注取脑组织。取小鼠脑组织石蜡切片,免疫组化方法检测各组小鼠脑组织中MALT1并用ELISA法检测血清IL-17表达。结果:EAE组与佐剂组的小鼠神经功能评分、体重、血清中IL-17含量和脑组织中MALT1蛋白阳性细胞数比较差异均有统计学意义(P0.05)。EAE组中24 d组小鼠的神经功能评分(2.50±0.55)分明显高于14 d组的(0.83±0.41)分和40 d组的(1.50±0.32)分,体重(17.04±0.41)g明显少于14 d组的(18.33±0.49)g和40 d组的(18.15±0.13)g,且血清中IL-17含量(288.00±26.45)pg/mL明显高于14 d组的(122.60±10.11)pg/mL和40 d组的(184.40±29.51)pg/mL,脑组织中MALT1蛋白阳性细胞数(183.80±9.25)个明显多于14 d组的(78.25±9.47)个和40 d组的(133.50±19.87)个,差异均有统计学意义(P0.05)。结论:EAE小鼠神经功能评分越高,血清中IL-17含量越高,MALT1表达也越多,提示MALT1参与了EAE小鼠的发病过程,其机制可能与MALT1在EAE小鼠上调血清IL-17表达有关。
[Abstract]:Objective: to investigate the expression of mucosa-associated lymphoid tissue transporter 1 (MMP1) and serum interleukin-17 (Interleukin-17) in (EAE) mice with experimental autoimmune encephalomyelitis. And to explore the role of both in the pathogenesis of EAE. To further explore whether MALTI can be used as a therapeutic target for multiple sclerosis (MS) in order to find a new treatment for MS. Methods: 36 C57BL/6 female mice were randomly divided into EAE group and adjuvant group (18 mice in each group). In EAE group, the EAE model was made by using the foam mixture of MOG and complete Freund's adjuvant, and the adjuvant group was only given Freund's adjuvant. The incidence of each animal was observed and the neurological function score was scored every 2 days. At the 14th day, 24 days after immunization, 6 mice in each group were randomly taken, and the brain tissues were taken from the heart and perfused with 4% paraformaldehyde. Paraffin sections of mouse brain tissue were taken and the expression of IL-17 in serum was detected by immunohistochemical method and ELISA method. Results: the neurological function score and body weight of mice in EAE group and adjuvant group, There were significant differences in the content of IL-17 in serum and the number of positive cells of MALT1 protein in brain tissue (P0.05). The scores of neurological function in 24 day group in). EAE group (2. 50 卤0. 55) were significantly higher than those in 14 day group (P0.05). The scores of 0.83 卤0.41 and 40 days were (1.50 卤0.32) and (1.50 卤0.32), respectively. Body weight (17.04 卤0.41) g was significantly lower than that in 14 d group (18.33 卤0.49) g and 40 d group (18.15 卤0.13) g. The content of IL-17 in serum (288.00 卤26.45) pg/mL was significantly higher than that in 14-day group (122.60 卤10.11) pg/mL and 40-day group (184.40 卤29.51) pg/mL,. The number of MALT1 positive cells in brain tissue (183.80 卤9.25) was significantly higher than that in 14-day group (78.25 卤9.47) and 40-day group (133.50 卤19.87) (P0.05). Conclusion: the higher the neurological function score of EAE mice, the higher the content of IL-17 in serum and the higher the expression of MALT1, suggesting that MALT1 is involved in the pathogenesis of EAE mice, and its mechanism may be related to the up-regulation of IL-17 expression by MALT1 in EAE mice.
【作者单位】：山西医科大学第一临床医学院;山西医科大学第一医院;
【基金】：山西省自然科学基金(2013011052-3)
【分类号】：R744

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