摘要
目的:探讨B细胞转录激活因子(BATF)对实验性自身免疫性脑脊髓膜炎(EAE)的调控机制及其与维甲酸相关核孤儿受体γt(RORγt)的关系。方法:30只雌性C57BL/6小鼠随机分为对照组、EAE组和EAE+甲泼尼龙(MP)组,每组10只,利用髓鞘少突细胞糖蛋白多肽35-55、完全弗氏佐剂和百日咳毒素诱导EAE组模型,EAE+MP组在EAE组模型基础上予MP治疗,自免疫当天起隔天进行Kono’s评分,免疫后第26天,ELISA检测血清IL-17水平,流式细胞术检测脾脏淋巴细胞中Th17表达,HE和LFB染色进行病理观察,RT-PCR检测脊髓组织BATF、RORγt mRNA表达。结果:与对照组相比,EAE组小鼠临床症状评分、IL-17、Th17/CD4~+、BATF和RORγt mRNA表达显著升高(均P<0.05),LFB蓝色占比明显降低(P<0.05),EAE小鼠的脊髓切片血管周围有明显的单核细胞浸润;与EAE组相比,EAE+MP组小鼠临床症状评分、IL-17、Th17/CD4~+、BATF和RORγt mRNA表达显著下降(均P<0.05),LFB蓝色占比明显提高(P<0.05),脊髓切片血管周围的单核细胞浸润不明显。结论:EAE小鼠体内BATF、IL-17、Th17/CD4~+细胞和RORγt表达上调,BATF分别与IL-17、Th17/CD4~+、RORγt表达呈正相关,BATF的上调可能是EAE炎症的重要因素,MP可能通过下调BATF、RORγt表达降低Th17的分化,减轻EAE小鼠的炎症反应。
Objective:To investigate regulatory mechanism of B cell transcription activating factor(BATF)on experimental autoimmune cerebrospinal meningitis(EAE)and its relationship with retinoic acid orphan nuclear receptor γt(RORγt).Methods:Thirty female C57BL/6 mice were randomly divided into control group,EAE group and EAE+methylprednisolone(MP)group,with10 mice in each group. EAE group was induced by myelin oligodendrocyte glycoprotein polypeptide35-55,complete Freund’s adjuvant and pertussis toxin. EAE+MP group was given MP on basis of EAE group treatment,Kono’s score was given every other day since the day of immunization. On the 26th day after immunization,level of IL-17 in serum was detected by ELISA,expression of Th17 in spleen lymphocytes was detected by flow cytometry,pathological observation was performed by HE and LFB staining,and expressions of BATF and RORγt mRNA in spinal cord were detected by RT-PCR.Results:Compared with control group,clinical symptom score,IL-17,Th17/CD4,BATF and RORγt mRNA expressions of EAE group were significantly increased(P<0.05),LFB blue burden was significantly decreased(P<0.05),and there was significant monocyte infiltration around blood vessels of spinal cord section of EAE group;compared with EAE group,in EAE+MP group,clinical symptom score,IL-17,Th17/CD4,BATF and RORγt mRNA expressions were decreased significantly(P<0.05),while LFB blue burden was increased significantly(P<0.05),and monocyte infiltration around blood vessels of spinal cord section was not obvious.Conclusion:In EAE mice,expressions of BATF,IL-17,Th17/CD4cells and RORγt are up-regulated,and there is a positive correlation among them. Increasing of BATF may be an important factor in EAE inflammation. MP may reduce the differentiation of Th17 by down-regulating expressions of BATF and RORγt,and reduce the inflammatory response of EAE mice.
作者
傅增辉
林再红
金艳
姜岩
刘晶
于绘丽
张广萍
FU Zenghui;LIN Zaihong;JIN Yan;JIANG Yan;LIU Jing;YU Huili;ZHANG Guangping(Department of Neurology,the Third Affiliated Hospital of Qiqihar Medical University,Qiqihar 161002,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2022年第14期1680-1684,共5页
Chinese Journal of Immunology
基金
齐齐哈尔医学科学院面上基金项目(QMSI2019M-24)资助。