慢性间歇性低压低氧对代谢综合征小鼠组蛋白乙酰化水平的影响  

Effects of Chronic Intermittent Hypobaric Hypoxia on Histone Acetylation Levels in Metabolic Syndrome Mice

作　　者：何岩涛 易先德 于孟鑫 姚庆杰 丘玉玲 王晶仪 陈怡凡 潘展鹏 王程 HE Yantao;YI Xiande;YU Mengxin;YAO Qingjie;QIU Yuling;WANG Jingyi;CHEN Yifan;PAN Zhanpeng;WANG Cheng(School of Clinical Medicine,Jilin Medical University,Jilin Province 132013,China;School of Pharmacy,Jilin Medical University,Jilin Province 132013,China;School of Basic Medical Sciences,Jilin Medical University,Jilin Province 132013,China)

机构地区：[1]吉林医药学院临床医学院,吉林吉林132013 [2]吉林医药学院药学院,吉林吉林132013 [3]吉林医药学院基础医学院,吉林吉林132013

出　　处：《吉林医药学院学报》2025年第1期1-6,67,共7页Journal of Jilin Medical University

基　　金：吉林省教育厅科学技术研究项目(JJKH20230541KJ);吉林医药学院2023年大学生创新创业训练项目(2023CXXL025)。

摘　　要：目的 探索代谢综合征(metabolic syndrome,MS)小鼠实施慢性间歇性低压低氧(chronic intermittent hypobaric hypoxia,CIHH)干预后肝组织组蛋白乙酰化水平的变化。方法 随机将40只C57BL/6J雄性小鼠平均分为NN/CON、CIHH/CON、NN/MS和CIHH/MS四组。NN/MS和CIHH/MS组小鼠用高脂高糖饲料+10%果糖溶液喂养16周,NN/CON和CIHH/CON小鼠同期用基础饲料+日常饮用水喂养。然后CIHH/CON和CIHH/MS组小鼠进行CIHH处理(模拟5000 m海拔高度,28 d,6 h/d)。常规测量体质量和腹围,无创血压计测量尾动脉收缩压(systolic arterial pressure,SAP),血糖仪检测空腹血糖(fasting blood glucose,FBG),酶联免疫法测定血清胰岛素并计算胰岛素抵抗指数(insulin resistance index,IRI),生化分析仪测量血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)和高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)含量,试剂盒检测低氧诱导因子-1ɑ(hypoxia inducible factor-1ɑ,HIF-1ɑ)含量以及组蛋白乙酰转移酶(histone acetyltransferase,HAT)和去乙酰化酶(histone deacetylase,HDAC)活力,蛋白质印记法检测组蛋白各亚基相对表达水平和特异性位点乙酰化水平。结果 与NN/CON组比较,NN/MS组小鼠腹围、FBG、SAP、IRI、TC、TG和LDL-C升高,HDL-C降低,HAT活力升高,HDAC活力降低,组蛋白各亚基均有部分特异性位点乙酰化水平升高(P<0.05)。与NN/MS组比较,CIHH/MS组小鼠血清HIF-1ɑ升高,腹围、FBG、SAP、IRI、TC、TG和LDL-C降低,HDL-C升高,HAT活力降低,HDAC活力升高,组蛋白各亚基均有部分特异性位点乙酰化水平降低(P<0.05)。发生乙酰化水平变化的特异性位点涉及H2A亚基中的K5位点,H2B亚基中的K15位点,H3亚基中的K4、K9、K14、K23、K27位点和H4亚基中的K5、K8、K12、K16位点。结论 CIHH可有效缓解MS小鼠的代谢紊乱症状,抑制HAT活力和恢复HDAC活力,降低MS小鼠肝组织Objective To explore the alterations in histone acetylation levels in liver tissue of mice with metabolic syndrome(MS)following chronic intermittent hypobaric hypoxia(CIHH)intervention.MethodsForty C57BL/6J male mice were randomly divided into NN/CON,CIHH/CON,NN/MS and CIHH/MS groups.Mice in NN/MS and CIHH/MS groups were fed with high-fat and high-sugar diet+10%fructose solution for 16 weeks,while Mice in NN/CON and CIHH/CON groups were fed with standard diet+regular drinking water concurrently.Then,mice in CIHH/CON and CIHH/MS groups were treated with CIHH(simulated 5000 m altitude,28 days,6 hours per day).Body weight and abdominal circumference(AC)were measured routinely.Systolic arterial pressure(SAP)was detected using a noninvasive sphygmomanometer.Fasting blood glucose(FBG)was detected using a glucometer,while fasting serum insulin was determined by an enzyme-linked immunosorbent assay for calculating insulin resistance index(IRI).Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected using a biochemical analyzer.Hypoxia-inducible factor(HIF)-1α contents and histone acetyltransferase(HAT)and deacetylase(HDAC)activities were determined using commercial kits.Relative expression levels of histone subunits and acetylation levels at specific sites were determined by western blotting.ResultsCompared with NN/CON group,Mice in NN/MS group showed an increase in AC,FBG,SAP,IRI,TC,TG and LDL-C,a decrease in HDL-C,enhanced HAT activity,reduced HDAC activity,and acetylation levels of the partial specific site in histone subunits increased(P<0.05).Compared with NN/MS group,Mice in CIHH/MS group showed a decrease in AC,FBG,SAP,IRI,TC,TG and LDL-C,an increase in HDL-C,reduced HAT activity,enhanced HDAC activity,and acetylation levels of the partial specific site in histone subunits decreased(P<0.05).The specific sites with altered acetylation levels included K5 site in H2A,K15site in H2B,K4,K9,K14,K23,K27 sites in H3,and K5,K8,K12,

关 键 词：慢性间歇性低压低氧 代谢综合征 表观遗传 组蛋白乙酰化 

分 类 号：Q142[生物学—生态学] R394.3[生物学—普通生物学]