白细胞介素12和18在P0_(180-199)特异性T细胞致神经炎中的协同增强效应  

Effects of the synergetical potentiation of interleukin-12 and interleukin-18 in neurosis induced by T cell lines specific for myelin-specific P0 protein peptides (P0_(180-199))

作　　者：王宇虹[1] 张惊宇[2] 张淑琴[2] 杨立斌[2] 

机构地区：[1]哈尔滨医科大学附属第一临床医学院神经内科,黑龙江省哈尔滨市150001 [2]吉林大学第一临床医学院神经内科,吉林省长春市130021

出　　处：《中国临床康复》2005年第33期58-60,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:观察白细胞介素12和18是否在P0180-199特异性T细胞过继的实验性自身免疫性神经炎中发挥协同增强作用。方法:实验于2003-03/2004-08在哈尔滨医科大学神经病理实验室完成。选取14～16周龄健康纯系雌性Lewis鼠50只。随机均分为5组,阴性对照组,白细胞介素12组,白细胞介素18组,白细胞介素12和18联合组,P0阳性对照组,每组10只。用白细胞介素12和/或18体外预孵育的P0180-199特异性T细胞过继动物,引发过继性实验性自身免疫性神经炎后,观察和评估单独组和联合组的临床症状和病理改变。由2个观察者采取双盲法,每日对每只鼠进行临床评分,分值为两个得分的平均数。结果:50只小鼠在实验过程中无死亡,全部进入结果分析。①20mg/L的P0180-199具有最强的T细胞增殖能力,可选择这个浓度体外扩增P0180-199T细胞系。②P0对照组的过继性实验性自身免疫性神经炎发病率低(2/10),白细胞介素12和18联合组的所有大鼠均有发病(10/10)。白细胞介素12和18联合组的病情严重,甚至有1只大鼠死于呼吸麻痹,发病时间和发病高峰时间均显著低于白细胞介素12组以及白细胞介素18组([2.6±0.8),(3.2±0.9),(3.4±0.9)d,t=2.7,P<0.05],[(5.8±1.4),(6.6±1.9),(8.1±1.8)d,t=2.7,P<0.05]。③白细胞介素12和18联合组病理表现为坐骨神经内的炎细胞的浸润数目增加和脱髓鞘的面积增加显著高于单独致敏的白细胞介素12组或白细胞介素18组,差异均有显著性意义([37.1±11.2),(19.1±6.1),(14.6±4.9)个/mm2,t=3.6,P<0.05];([3.2±0.6),(2.3±0.3),(2.0±0.3),t=3.1,P<0.05]。结论:白细胞介素12和18联合孵育的P0180-199特异性T细胞具有更强的致神经炎作用,临床表现为更高的发病率,更严重的神经炎和更延迟的恢复期。AIM： To observe whether interleukin-12 （IL-12） and interleukin-18 （IL- 18） have the synergetic potentiation in T cell lines specific for myelinspecific P0 protein peptides （P0 180-199） adopted experimental autoimmune neuritis. METHODS： The experiment was completed in the laboratory of neuropathology, Harbin Medical University from Marcy 2003 to August 2004. Fifty healthy female Lewis rats of 14-16 weeks old were randomized into 5 groups with 10 rats in each group： negative control group, IL-12 group, IL-18 group, IL-12＋IL-18 group, and P0 positive control group. The rats were adopted by the （P0 180-199） specific T cells, which were in vitro preincubated with IL-12 and/or IL-18, and the clinical symptoms and pathological changes in the groups were observed and evaluated after the adoptive experimental autoimmune neurosis was induced. The clinical score was performed in each rat every day by two observers with the double-blinded method, and the average value was taken as the score. RFSULTS： No rat died during the trial. ① The incidence rate of adoptive autoimmune neuritis was the lowest in the P0 control group （2/10）, and the highest in the IL-12＋IL-18 group （1040）. ② In the IL-12＋IL-18 group, the disease was severe, and 1 rat died of respiratory paralysis, and the attack time and peak attack time were significantly lower than those in the IL-12 group and IL-18 group [（2.6±0.8）, （3.2±0.9）, （3.4±0.9） days, t=2.7, P 〈 0.05; （5.8±1.4）, （6.6±1.9）, （8.1±1.8） days, t=2.7, P 〈 0.05]. ③ In the IL- 12＋IL-18 group, the pathological manifestations were the increased number of the infiltration of inflammatory cells in sciatic nerve and the increased area of demyelination, which were significantly higher than those in the IL- 12 group or IL-18 group [（37.1±11.2）, （19.1±6.1）, （14.6±4.9） cells/mm^2, t= 3.6, P〈 0.05; （3.2：e0.6）, （2.3±0.3）, （2.0±0.3）, t=3.1, P〈 0.05]. CONCLUSION： IL-12 and IL-18 incubated （P0 180-1

关 键 词：白细胞介素12 白细胞介素18 神经炎 药物协同作用 

分 类 号：R745[医药卫生—神经病学与精神病学]