microRNA-193b和microRNA-141在脓毒血症休克小鼠基因启动子区的甲基化状态  

The promoter methylation of microRNA-193b and microRNA-141 gene in septic shock mice

作　　者：吴思思[1] 李雪 李如利 蒋维[2,3] 汪香秀 汪潇潇 WU Si-si;LI Xue;LI Ru-li;JIANG Wei;WANG Xiang-xiu;WANG Xiao-xiao(Core Facility,West China Hospital,Sichuan University,Chengdu 610041;State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610041;Molecular Medicine Research Center,West China Hospital,Sichuan University,Chengdu 610041;Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital&Chongqing Cancer Institute&Chongqing Cancer Hospital,Chongqing 400030,China)

机构地区：[1]四川大学华西医院公共实验技术中心,成都610041 [2]四川大学生物治疗国家重点实验室,成都610041 [3]四川大学华西医院分子医学研究中心,成都610041 [4]重庆大学附属肿瘤医院重庆市肿瘤研究所重庆市肿瘤医院肿瘤转移与个体化诊治转化研究重庆市重点实验室,重庆400030

出　　处：《生物学杂志》2020年第2期14-17,共4页Journal of Biology

基　　金：国家自然科学基金(81670249)。

摘　　要：为了探究microRNA-193b和microRNA-141在脓毒血症休克小鼠的受累器官的基因启动子区甲基化及病理生理学意义,利用盲肠结扎穿刺(CLP)小鼠脓毒血症休克晚期模型,采用多导生理仪检测心功能,自动生化仪检测血糖和血乳酸水平,亚硝酸氢盐测序(BSP法)分别检测小鼠心脏、肝脏、肺及小肠的microRNA-193b和microRNA-141的基因启动子区甲基化。microRNA-193b基因克隆测序结果表明,休克晚期小鼠心脏组织其CpG岛的甲基化程度明显升高,甲基化频率为23.9%,高于正常组1.9%(P<0.05);microRNA-141基因克隆测序结果显示,休克晚期小鼠肺、小肠组织其CpG岛的甲基化程度明显升高,甲基化频率分别为31.2%和36.9%,高于正常组织3.4%(P<0.01)和4.6%(P<0.01)。结果表明在脓毒血症休克时,小鼠出现心功能障碍和代谢紊乱,microRNA-193b和microRNA-141的基因启动子区CpG岛甲基化,这可能是microRNA-193b和microRNA-141的表达水平变化的原因,并提示它们可能通过调节下游炎症相关靶蛋白的表达,继而调节感染性休克的病理生理过程。microRNA-193b和microRNA-141可能为感染性疾病早期诊断、治疗的新标志物和新靶点。To investigate the hypermethylation status of microRNA-193b and microRNA-141 in septic shock mice,with the use of a mouse septic model induced by cecal ligation and puncture,the cardiac function was further detected with a multi-channel physiological signal acquisition system.The methylation statuses of both microRNA-193b and microRNA-141 in heart,liver,lung and small intestine tissues were detected by using bisulfite sequencing PCR and a real-time PCR method,respectively.The results indicated that the cardiac function was significantly impaired in the mice with late stage of sepsis shock.The methylation rate of microRNA-193b in heart tissue of the septic mice was 23.9%,1.9%higher than that in normal tissue(P<0.05).The methylation rates of microRNA-141 in lung and intestine tissue of the septic mice were 31.2%and 36.9%,3.4%and 4.6%higher than those in normal tissue(P<0.01),respectively.CpG islands in microRNA-193b and microRNA-141 gene promoter region were hypermethylated,which might be the reason for the changes in the expression of microRNA-193b and microRNA-141,suggesting that both of them might participate in the regulation on the pathophysiological state by regulating the protein expression of their downstream inflammation-related factors.Both microRNA-193b and microRNA-141 might be new biomarkers and targets for the infectious diseases diagnose and therapy.

关 键 词：脓毒血症 microRNA-193b microRNA-141 甲基化 

分 类 号：Q74[生物学—分子生物学]