Notch信号通路在新生鼠高氧暴露致少突胶质细胞成熟障碍中的作用  

Role of Notch signaling in hyperoxia-induced oligodendrocyte maturation disorder of neonatal mice

作　　者：刘光建[1] 郭冉[1] 杜敏[1] 刘杨[1] 刘剑霞[1] 徐颖[1] 

机构地区：[1]重庆医科大学附属儿童医院麻醉科,儿童发育疾病研究省部共建教育部重点实验室,儿科学重庆市重点实验室,重庆400014

出　　处：《第三军医大学学报》2015年第17期1766-1770,共5页Journal of Third Military Medical University

基　　金：国家临床重点专科建设项目(2013544)~~

摘　　要：目的探讨Notch信号通路在新生鼠高氧暴露致少突胶质细胞成熟障碍中的作用。方法取C57BL/10J新生3 d(P3)小鼠64只,分为空气对照组(C)、空气+DAPT组(C+DAPT)、高氧组(H)、DAPT预处理高氧暴露组(H+DAPT);H组予以高氧暴露48 h,H+DAPT组采用Notch信号特异抑制剂DAPT(10 mg/kg)腹腔注射1 h后高氧暴露48 h。生后5 d(P5)断头取脑。Real-time PCR检测Notch1、Jagged1、Hes1及Hes5表达变化。生后12 d(P12)取脑,HE染色观察脑白质形态学变化;免疫荧光化学染色检测成熟少突胶质细胞表达;Western blot定量检测MBP蛋白的表达量。结果与C组比较,H组小鼠脑组织明显水肿,Notch1、Jagged1、Hes1及Hes5 mRNA的表达均增高(P<0.05);与H组比较,H+DAPT组Notch1、Jagged1 mRNA表达明显增强(P<0.05),Hes1及Hes5 mRNA表达显著降低(P<0.05);免疫荧光和Western blot结果均显示H组MBP表达低于C组(P<0.05);而与H组比较,H+DAPT组MBP表达显著增多(P<0.05)。结论 Notch信号通路参与了高氧暴露致新生鼠脑白质损伤过程,其机制可能与影响少突胶质细胞的成熟有关。Objective To investigate the effect of Notch signaling pathway on hyperoxia-induced oligodendrocyte maturation disorder in the brain tissue of neonatal mice. Methods Sixty-four C57 BL /10 J neonatal mice were randomly divided into air control group,air ＋ DAPT（ Notch signaling pathway blocker,10 mg / kg） group,hyperoxia group（ hyperoxia exposure for 48 h）,and hyperoxia ＋ DAPT group（ hyperoxia exposure for 48 h after 10 mg / kg DAPT treatment）. All neonatal mice were killed,and the brains were taken out to detect the mRNA expression changes of Notch1,Jagged1,Hes1 and Hes5 by real-time PCR in the 5th day after birth. In the 12 th day after birth,oligodendrocytes were identified by immunofluorescent staining,and myelin basic protein（ MBP） expression was detected by Western blotting. Results The hyperoxia group showed brain injury characterized by inhibition of brain development. There were significant differences in mRNA expressions of Notch1 and Jagged1 between the hyperoxia ＋ DAPT group and the hyperoxia group（ P 0. 05）,and the mRNA expressions of Hes1 and Hes5 in the hyperoxia-treated groups were significantly lower than those in the control group（ P 0. 05）. Higher expression of MBP was observed in the hyperoxia ＋ DAPT group compared with the hyperoxial group（ P 0. 05）. Compared with the control group,the MBP expression was significantly decreased in the hyperoxia group（ P 0. 05）. Conclusion Notch signaling pathway involves in hyperoxia-induced brain damage in the neonatal mice,which is probably associated with the maturation of oligodendrocytes.

关 键 词：高氧 DAPT 脑损伤 NOTCH信号通路 少突胶质细胞成熟 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]