m^(6)A RNA甲基化修饰在颅脑损伤模型大鼠坏死性凋亡中的作用  

Role of m^(6)A RNA methylation modification in necrotic apoptosis in a rat model of brain injury

作　　者：林树楷 刘仲海[1] 刘珍[1] 蔡金城 魏入廷 Lin Shukai;Liu Zhonghai;Liu Zhen;Cai Jincheng;Wei Ruting(Department of Neurosurgery,Sanya Central Hospital(Hainan Third People’s Hospital),Sanya 572000,Hainan Province,China;Department of Neurosurgery,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518005,Guangdong Province,China;Department of Neurosurgery,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou Province,China)

机构地区：[1]三亚中心医院(海南省第三人民医院)神经外科,海南省三亚市572000 [2]深圳市中医院神经外科,广东省深圳市518005 [3]贵州医科大学附属医院神经外科,贵州省贵阳市550004

出　　处：《中国组织工程研究》2023年第20期3167-3172,共6页Chinese Journal of Tissue Engineering Research

摘　　要：背景:哺乳动物中枢神经系统损伤依赖N6-甲基腺苷(m^(6)A)的调节,并与坏死性凋亡密切相关。目前在大鼠创伤性颅脑损伤中,m^(6)A RNA甲基化修饰与创伤性颅脑损伤坏死性凋亡的关系尚未被研究。目的:探讨m^(6)A RNA甲基化修饰与创伤性颅脑损伤大鼠坏死性凋亡的关系,为颅脑损伤坏死性凋亡的发生发展及预后的分子机制提供实验依据。方法:选取SPF级SD雄性大鼠30只,随机分为假手术组、创伤性颅脑损伤组和NSC118218(STAT1抑制剂)组,各10只。后2组通过改良Feeney法建立颅脑损伤模型,假手术组仅暴露脑硬膜,不进行颅脑打击。颅脑损伤6 h后检测各组大鼠大脑皮质炎症因子肿瘤坏死因子ɑ、白细胞介素6、白细胞介素1β、白细胞介素10和高迁移率族蛋白B1表达水平以及脑含水量,检测YTH结构域家族蛋白2、总m^(6)A RNA甲基化修饰水平、STAT1和JAK1的表达水平。结果与结论:①创伤性颅脑损伤组和NSC118218组炎症因子水平和脑含水量明显高于假手术组,m^(6)A RNA甲基化修饰比例和YTHDF2表达水平明显低于假手术组,JAK1和STAT1的表达水平明显高于假手术组(P<0.05);②与创伤性颅脑损伤组相比,NSC118218组炎症因子水平和脑含水量明显降低,m^(6)A RNA甲基化修饰比例和YTH结构域家族蛋白2表达水平明显升高,JAK1和STAT1的mRNA及蛋白表达水平明显降低(P<0.05);③提示颅脑损伤后m^(6)A RNA甲基化修饰比例降低,YTH结构域家族蛋白2表达水平下降,激活JAK/STAT信号通路,增加JAK1和STAT1的表达,促进细胞坏死性凋亡。BACKGROUND:Mammalian central nervous system injury is dependent on the regulation of N6-methyladenosine(m^(6)A)and is closely associated with necrotic apoptosis.At present,the relationship between m^(6)A RNA methylation modification and necrotic apoptosis in rat models of traumatic brain injury has not been studied.OBJECTION:To study the relationship between m^(6)A RNA methylation and necrotic apoptosis in a rabbit brain injury model and to provide experimental basis for the molecular mechanism of occurrence,development and prognosis of necrotic apoptosis following craniocerebral injury.METHODS:A total of 30 SPF male Sprague-Dawley rats were selected and randomized into sham operation group(n=10),traumatic brain injury group(n=10),and signal transducer and activator of transcription 1(STAT1)inhibitor(NSC118218)group(n=10).The brain injury model was established using the modified Feeney method in the latter two groups,while the dura mater in the sham operation group was only exposed without striking.The levels of inflammatory factors,tumor necrosis factorɑ,interleukin-6,interleukin-1β,interleukin-10,and high mobility group box 1 in the cerebral cortex of rats and brain water content were detected at 6 hours after brain injury.At the same time,the methylation level of total m^(6)A RNA and the mRNA and protein expression levels of YTH domain family protein family 2(YTHDF2),JAK1 and STAT1 were detected.RESULTS AND CONCLUSION:The levels of inflammatory factors,brain water content,and the expression of JAK1 and STAT1 in the traumatic brain injury group and NSC118218 group were significantly higher than those in sham operation group,while the proportion of m^(6)A RNA methylation and the expression level of YTHDF2 were significantly lower than those in the sham operation group(P<0.05).The levels of inflammatory factors,brain water content,and the mRNA and protein expressions of JAK1 and STAT1 in the NSC118218 group were significantly lower than those in the traumatic brain injury group,while the proportion of m^(6)A RN

关 键 词：创伤性颅脑损伤 m^(6)A RNA甲基化 坏死性凋亡 JAK/STAT 动物模型 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R651.15