胸腺内注射脑抗原致免疫耐受治疗大鼠手术脑损伤  

Treatment of surgical brain injury with immune tolerance induced by intrathymic injection of brain antigen

作　　者：杨伟健[1] 王宏[2] 张博[2] 刘保龙[2] 刘勇[2] 闫华[2,3] 

机构地区：[1]天津医科大学研究生院,300070 [2]天津市环湖医院神经外科 [3]天津市脑血管与神经变性重点实验室

出　　处：《中华创伤杂志》2016年第6期542-546,共5页Chinese Journal of Trauma

基　　金：天津市自然科学基金（13JCYBJC21100）;天津市科技支撑计划（13ZCZDSY01600）

摘　　要：目的探讨大鼠胸腺内注射髓鞘碱性蛋白（MBP）诱导免疫耐受治疗手术脑损伤（SBI）的疗效。方法24只sD雄性大鼠按随机数字表法分为实验组、对照组及假手术组，每组8只。实验组和对照组建立大鼠SBI模型并暴露胸腺，分别注射MBP和等渗盐水；假手术组只开骨窗，并保持硬脑膜完整，暴露胸腺空针穿刺。分别于术后1，3，7，14，21d对各组进行改良神经功能缺陷评分（MNSS），头颅MRI检测脑水肿体积，酶联免疫吸附法检测外周血促炎因子白细胞介素（IL）-2、抗炎因子IL-4浓度，流式细胞仪检测外周血CD4＋／CD8＋T细胞比值。结果术后3，7，14，21d，实验组MNSS显著低于对照组（P〈0．05），且于术后21d恢复至假手术组水平（P〉0．05），但对照组未恢复至假手术组水平（P〈0．05）。术后1，3，7，14，21d，实验组脑水肿体积显著小于对照组（P〈0．05），但实验组及对照组脑水肿体积未恢复至假手术组水平（P〈0．05）。术后3，7，1dd，实验组IL-2浓度低于对照组（P〈0．05）、IL-4浓度高于对照组（P〈0．05）。术后1，3，7，14，21d，实验组IL-2浓度、对照组IL-4浓度与假手术组差异无统计学意义（P〉0．05）。术后1，7，14d，实验组与对照组外周血CD4＋／CD8＋T细胞比值差异有统计学意义（P〈0．05），且实验组于术后7d恢复至假手术组水平（P〉0．05），对照组于术后21d恢复至假手术组水平（P〉0．05）。结论大鼠胸腺内注射MBP诱导免疫耐受有助于减轻SBI引起的脑神经功能缺陷和脑水肿体积，可促进术后脑损伤的恢复。Objective To determine the effect of induction of immune tolerance by intrathymic injection of myelin basic protein （MBP） for treatment of surgical brain injury （SBI） in rats. Methods Twenty-four male SD rats were divided into experimental group, control group and sham group with 8 rats each, according to the random number table. SBI model was established in experimental group and control group. Thymuses were exposed and injected with MBP （experimental group ） or saline （ control group） respectively. Sham group received craniotomy without durotomy and thymus paracentesis. Modified neurological severity score （MNSS） , cerebral edema volume, levels of peripheral blood pro- inflammatory cytokine intedeukin （IL）-2 and anti-inflammatory cytokine IL-4, and CD4 ＋/CD8 ＋ T-cell ratio were measured at postoperative 1, 3, 7, 14 and 21 d. Results MNSS between control and experimental groups differed significantly at each time point （ P 〈 0.05 ）. Compared to sham group, MNSS in experimental group was recovered the same value at 21 d （ P 〉 0. 05 ） , but in control groupremained high over the study （P 〈 0. 05）. Less cerebral edema was observed in control and experimental groups than in control group at each time point （P 〈0. 05）, but all were lower than these in sham group （P 〈 0. 05 ）. Lower IL-2 concentrations and higher IL-4 concentrations were observed in experimental group than in control group at 3, 7 and 14 d （ P 〈 0. 05 ）. Compared to sham group, IL-2 concentrations in experimental group and IL-4 concentrations in control group revealed no significant differences at each time point （P 〉0.05 ）. CD4＋/CD8 ＋ T-cell ratio between experimental group and control group revealed significant difference at 1, 7 and 14 d （P 〈0.05）. CD4 ＋/CD8 ＋ T-cell ratio in experimental group and control group recovered to the same level in sham group at 7 and 21 d （P 〉 0. 05）. Conclusion Induction of immune tolerance through intrathymic injection of MBP can

关 键 词：胸腺 髓磷脂碱性蛋白质类 免疫耐受 手术脑损伤 

分 类 号：R651.15[医药卫生—外科学]