ChREBP基因启动子甲基化调控TLRs/MyD88/NF-κB信号通路对2型糖尿病发病机制的研究  

Study on the pathogenesis of type 2 diabetes mellitus by methylation of ChREBP gene promoter regulating TLRs/MyDD8/NF-κB signaling pathway

作　　者：王欣[1] 皇甫卫忠[1] 赵丰[1] WANG Xin;HUANGFU Wei-zhong;ZHAO Feng(Department of General Practice,Affiliated Hospital of Inner Mongolia Medical University,Hohhot Inner Mongolia 010050,China)

机构地区：[1]内蒙古医科大学附属医院全科医学科,内蒙古呼和浩特010050

出　　处：《临床和实验医学杂志》2023年第3期270-273,共4页Journal of Clinical and Experimental Medicine

基　　金：内蒙古自治区自然科学基金项目(编号:2019MS08165);内蒙古医科大学科技百万工程联合项目[编号:YKD2018KJBW(LH)027]。

摘　　要：目的研究探讨碳水化合物反应原件结合蛋白(ChREBP)基因启动子的甲基化水平在2型糖尿病(T2DM)发病机制中的作用,同时验证CD14+类白细胞参与T2DM的发病机制。方法使用单纯随机抽样方法选取2019年1月至6月间内蒙古医科大学附属医院收治的T2DM患者40例(T2DM组),同时选取正常体检者20名(对照组)作为研究对象纳入分析。留取外周血测定CD14+单核细胞Toll样受体2(TLR2)、依赖髓样分化因子88(MyD88)、核因子κB(NF-κB)等相关因子表达水平,并比对正常人和T2DM患者全血DNA中ChREBP基因启动子的甲基化水平。结果T2DM组ChREBP甲基化水平均高于对照组,差异有统计学意义(P<0.05)。T2DM组TLR4、MyD88为1.23±0.32、1.86±0.36,均显著高于对照组(0.97±0.36、0.84±0.33),NF-κBP65、磷酸化IκB-ɑ为1.37±0.31、0.87±0.29,均显著低于对照组(1.95±0.31、1.50±0.37),差异均有统计学意义(P<0.05)。进一步分析可见,ChREBP甲基化水平与TLR4、MyD88呈正相关(r=0.334、0.387,P<0.05),与NF-κBP65和磷酸化IκB-ɑ呈负相关(r=-0.298、-0.326,P<0.05)。结论ChREBP基因启动子的甲基化水平增高与T2DM发病相关联,同时CD14+类白细胞参与T2DM的发生,提示ChREBP基因启动子甲基化可能通过调控TLRs/MyD88/NF-κB信号通路参与T2DM的发生过程。Objective To investigate the role of the methylation level of carbohydrate reactive element binding protein(ChREBP)gene promoter in the pathogenesis of diabetes and to verify that CD14+leukocytes participate in the pathogenesis of type 2 diabetes mellitus(T2DM);in order to provide a theoretical basis for gene diagnosis and treatment in the future.Methods A total of 40 T2DM patients in the Affiliated Hospital of Inner Mongolia Medical University from January to June 2019 were selected by pure random sampling method(T2DM group),and 20 normal physical examination subjects(control group)were selected for analysis.The expression levels of Toll like receptor-2(TLR2),medullary differentiation factor dependent 88(MyD88),nuclear factorκB(NF-κB)and other related factors in CD14+mononuclear cells were measured in peripheral blood,and the methylation levels of ChREBP gene promoter in whole blood DNA of normal people and type 2 diabetes patients were compared.Results ChREBP methylated water in T2DM group was significantly higher than that in control group,the difference was statistically significant(P<0.05).TLR4 and MyD88 in T2DM group were 1.23±0.32 and 1.86±0.36,which were significantly higher than those in control group(0.97±0.36,0.84±0.33),NF-κBP65 and phosphorylated IκB-ɑwere 1.37±0.31,0.87±0.29,which were significantly lower than those in the control group(1.95±0.31,1.50±0.37),the differences were statistically significant(P<0.05).Further analysis showed that ChREBP methylation level was positively correlated with TLR4,MyD88(r=0.334,0.387,P<0.05),was negatively correlated with NF-κBP65 and phosphorylated IκB-ɑ(r=-0.298,-0.326,P<0.05).Conclusion The increased methylation level of ChREBP gene promoter is associated with the pathogenesis of T2DM.At the same time,CD14+leukocytes participate in the pathogenesis of T2DM,suggesting that ChREBP gene promoter methylation may participate in the pathogenesis of T2DM through regulating TLRs/MyD88/NF-κB signaling pathway.

关 键 词：ChREBP基因 甲基化 2型糖尿病 CD14+类白细胞 

分 类 号：R587.1[医药卫生—内分泌]