下丘脑内侧基底部神经元HIF2α敲低对小鼠体重和能量代谢率的影响  

Effect of HIF2α knockdown in the neurons of mediobasal hypothalamus on body weight and energy metabolism in mice

作　　者：迪丽胡买尔·多力坤 艾孜买提·肉孜江 马丽娟[1] 郭海[2] 姚巧玲[1] Dilihumaier Duolikun;Aizimaiti Rouzijiang;MA Lijuan;GUO Hai;YAO Qiaoling(Room of Physiology,School of Basic Medical Sciences,Xinjiang Medical University,Xinjiang Uygur Autonomous Region,Urumqi 830011,China;Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Xinjiang Uygur Autonomous Region,Urumqi 830011,China)

机构地区：[1]新疆医科大学基础医学院生理教研室,新疆乌鲁木齐830011 [2]新疆医科大学第一附属医院麻醉科,新疆乌鲁木齐830011

出　　处：《中国医药导报》2023年第20期10-16,22,共8页China Medical Herald

基　　金：国家自然科学基金资助项目(81560020、81960162);省部共建国家重点实验室中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2022-4)。

摘　　要：目的探究下丘脑内侧基底部神经元缺氧诱导因子2α(HIF2α)敲低对小鼠体重、进食量和能量代谢的影响。方法选择16只雄性HIF2αflox/flox转基因小鼠,分为在下丘脑内侧基底部注射AAV-hSyn-GFP病毒的对照组(n=8)和注射AAV-hSyn-cre-GFP病毒的HIF2α敲低组(n=8)。两组小鼠均给予普通饲料喂养,每3天称量体重和进食量。4周后利用核磁共振分析仪和代谢笼分别检测小鼠体成分以及能量代谢率。结果对照组小鼠第18~30天体重均高于第3天,差异有统计学意义(P<0.05);HIF2α敲低组小鼠第9~30天体重高于第3天,差异有统计学意义(P<0.05);HIF2α敲低组小鼠第15~30天体重高于对照组,差异有统计学意义(P<0.05)。对照组小鼠第12~30天进食量与第3天比较,差异有统计学意义(P<0.05);HIF2α敲低组小鼠第9~30天进食量均高于第3天,差异有统计学意义(P<0.05);HIF2α敲低组小鼠第9~30天进食量高于对照组,差异有统计学意义(P<0.05)。HIF2α敲低组体脂重、体液重、瘦体质高于对照组(P<0.01)。敲低组白天和夜间耗氧量(VO2)低于对照组(P<0.05或P<0.01);对照组夜间VO2高于白天(P<0.05);HIF2α敲低组夜间与白天VO2比较,差异无统计学意义(P>0.05)。HIF2α敲低组夜间二氧化碳产出量(VCO_(2))低于对照组(P<0.05),两组白天VCO_(2)比较,差异无统计学意义(P>0.05);对照组夜间VCO_(2)高于白天(P<0.05);HIF2α敲低组夜间与白天VCO_(2)比较,差异无统计学意义(P>0.05)。HIF2α敲低组白天呼吸熵(RER)高于对照组(P<0.05)。两组夜间与白天RER比较,差异无统计学意义(P>0.05)。HIF2α敲低组白天与夜间能量消耗(EE)低于对照组(P<0.05或P<0.01)。对照组夜间EE高于白天,差异有统计学意义(P<0.05)。HIF2α敲低组夜间与白天EE比较,差异无统计学意义(P>0.05)。HIF2α敲低组夜间活动量低于对照组(P<0.05),而两组白天活动量比较,差异无统计学意义(P>0.05)。对照组夜间活动量高于白天(P<0.05);HIF2Objective To investigate the effects of hypoxia-inducible factor 2α(HIF2α)knockdown in the neurons of the mediobasal hypothalamus on body weight,food intake and energy metabolism in mice.Methods Sixteen HIF2αflox/flox transgenic male mice were selected and they were divided into control group injected with AAV-hSyn-GFP virus at the mediobasal of the hypothalamus(n=8)and HIF2αknockdown group injected with AAV-hSyn-cre-GFP virus groups of mice were fed with normal chow and their body weight and food intake were weighed every three days.After four weeks,the body composition and energy metabolic rate of mice were measured by nuclear magnetic resonance analyzer and metabolic cage.Results The body weight of mice in the control group on days 18 to 30 was higher than that on days 3,the difference was statistically significant(P<0.05).The body weight of mice in HIF2αknockout group on days 9 to 30 was higher than that on days 3,the difference was statistically significant(P<0.05);the body weight of mice in HIF2αknockdown group was higher than that in control group on the 15th to 30th day,and the difference was statistically significant(P<0.05).The food intake of mice in the control group on the 12th to 30th day was significantly different from that on the 3rd day(P<0.05).The food intake of mice in HIF2αknockout group on days 9 to 30 was higher than that on days 3,and the difference was statistically significant(P<0.05).The food intake of mice in HIF2αknock-down group was higher than that in control group from 9 to 30 days,and the difference was statistically significant(P<0.05).Body fat weight,body fluid weight and lean body mass in HIF2αknockout group were higher than those in control group(P<0.01).The oxygen consumption(VO_(2))during the day and night in the knockdown group was lower than that in the control group(P<0.05 or P<0.01);in control group,VO_(2) at night was higher than that at day(P<0.05).There was no significant difference in VO_(2) between HIF2αknockdown group at night and daytime(P>0.05).The carbo

关 键 词：下丘脑 缺氧诱导因子2α 体重 进食量 能量代谢 

分 类 号：R332[医药卫生—人体生理学]