微RNA-219通过ERK1/2通路改善炎症所致新生SD大鼠脑内少突胶质细胞成熟障碍  

MicroRNA-219 promotes oligodendrocyte maturation through ERK 1/2 signaling pathway in inflammation model of neonatal SD rats

作　　者：张绍卿 杜敏[1,3] 刘兰[1,4] 徐颖[1,2] ZHANG Shaoqing;DU Min;LIU Lan;XU Ying(Department of Anesthesiology,Children’s Hospital of Chongqing Medical University,Chongqing 400014,China;National Clinical Research Center for Child Health and Disorders,Chongqing 400014,China;Key Laboratory of Child Development and Disorders of Ministry of Education,Chongqing 400014,China;Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院麻醉科,重庆400014 [2]国家儿童健康与疾病临床医学研究中心,重庆400014 [3]儿童发育疾病研究教育部重点实验室,重庆400014 [4]儿科学重庆市重点实验室,重庆400014

出　　处：《海军军医大学学报》2023年第12期1429-1434,共6页Academic Journal of Naval Medical University

基　　金：重庆市科学技术委员会民生项目(cstc2018jscx-msybX0104).

摘　　要：目的建立新生SD大鼠炎症模型,初步探究微RNA-219(miR-219)促进少突胶质细胞成熟的机制。方法将60只SD大鼠随机分为对照组、脂多糖(LPS)组(LPS 0.15 mg/kg腹腔注射)、LPS+miR-219 agomir组(LPS 0.15 mg/kg腹腔注射,miR-219 agomir 3μL侧脑室注射)、miR-219 antagomir组(miR-219 antagomir 3μL侧脑室注射)和LPS+miR-219 agomir+U0126组(LPS 0.15 mg/kg腹腔注射,miR-219 agomir 3μL侧脑室注射,U012630 mg/kg腹腔注射)。于大鼠出生第7天和第14天处死后取脑组织,采用qPCR检测脑组织中miR-219及炎症因子IL-1β、TNF-α的mRNA表达水平,蛋白质印迹法检测少突胶质细胞成熟标志物髓鞘碱性磷脂蛋白(MBP)和ERK 1/2表达水平,免疫荧光检测大鼠胼胝体少突胶质细胞的数量。结果与对照组相比,大鼠腹腔注射LPS后脑组织内IL-1β、TNF-αmRNA表达均升高(P<0.01),miR-219表达减少(P<0.01)。与LPS组相比,在用miR-219 agomir提升大鼠脑内miR-219的表达后MBP和ERK 1/2蛋白表达均增加(P<0.01),胼胝体少突胶质细胞数量增加。与对照组相比,在用miR-219 antagomir降低大鼠脑内miR-219的表达后,MBP和ERK 1/2蛋白表达均减少(P<0.01),胼胝体少突胶质细胞数量减少。用ERK 1/2通路抑制剂U0126处理后,miR-219对少突胶质细胞的促成熟作用受到了抑制(P<0.01)。结论在大鼠脑内miR-219对少突胶质细胞的促成熟作用是通过ERK 1/2通路发挥作用的。Objective To establish an inflammation model in neonatal SD rats and to explore the mechanism by which microRNA-219(miR-219)promotes oligodendrocyte maturation.Methods Sixty SD rats were randomly assigned to control group,lipopolysaccharide[LPS]group(LPS 0.15 mg/kg,intraperitoneal injection),LPS+miR-219 agomir group(LPS 0.15 mg/kg,intraperitoneal injection;miR-219 agomir 3μL,intraventricular injection),miR-219 antagomir group(miR-219 antagomir 3μL,intraventricular injection),or LPS+miR-219 agomir+U0126 group(LPS 0.15 mg/kg,intraperitoneal injection;miR-219 agomir 3μL,intraventricular injection;U012630 mg/kg,intraperitoneal injection).The th th rats were sacrified on the 7 and 14 day of life and the brain tissue was harvested.The expression levels of miR-219 and inflammatory factors interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)mRNA were detected by quantitative polymerase chain reaction.The expression levels of myelin basic protein(MBP)and extracellular signal-regulated kinase 1/2(ERK 1/2)were detected by Western blotting.The number of oligodendrocytes in the corpus callosum was observed by immunofluorescence.Results Compared with the control group,the expression levels of IL-1βand TNF-αmRNA were significantly increased after intraperitoneal injection of LPS in rats(both P<0.01),and the expression of miR-219 was significantly decreased(P<0.01).Compared with the LPS group,the expression levels of MBP and ERK 1/2 were significantly increased after miR-219 agomir was used to enhance the expression of miR-219 in the brain of rats(both P<0.01),with increased oligodendrocytes in the corpus callosum.Compared with the control group,the expression levels of MBP and ERK 1/2 were significantly decreased after miR-219 antagomir was used to reduce the expression of miR-219 in the brain of rats(both P<0.01),with decreased oligodendrocytes in the corpus callosum.After treatment with the ERK 1/2 pathway inhibitor U0126,the maturation promoting effect of miR-219 on oligodendrocytes was significantly inhibited

关 键 词：炎症 脑白质损伤 微RNA-219 细胞外信号调控的激酶 少突胶质细胞 

分 类 号：R741[医药卫生—神经病学与精神病学]