电损毁下丘脑腹内侧核与弓状核致大鼠肥胖模型的建立及其评价  

Establishment and evaluation of rat obesity model induced by electrical damage of ventromedial hypothalamic nucleus and arcuate nucleus

作　　者：彭君洁 冯展鹏 王兴勤 欧毅超 周明锋 武广森 龚浩东 李凯 牛培荣 刘裕盛 江建荣 漆松涛[1] Peng Junjie;Feng Zhanpeng;Wang Xingqin;Ou Yichao;Zhou Mingfeng;Wu Guangsen;Gong Haodong;Li Kai;Niu Peirong;Liu Yusheng;Jiang Jianrong;Qi Songtao(Department of Neurosurgery,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;First Clinical Medical College,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学南方医院神经外科,广州510515 [2]南方医科大学第一临床医学院临床医学,广州510515

出　　处：《中华行为医学与脑科学杂志》2020年第7期659-665,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目(81900709);广州市科技计划项目(201902020017);南方医科大学南方医院院长基金项目(2019C001,2019C016);大学生创新创业训练计划项目(B819NF2031-S201912121091)。

摘　　要：目的:通过两点法电损毁下丘脑腹内侧核和弓状核构建下丘脑性肥胖大鼠模型。方法:取成年雄性SD大鼠20只,按随机数字表法均分为模型组和对照组,使用1根25 GA(0.45 mm)实心铁针,针体涂上绝缘层,尖端暴露0.5 mm导电区域,参照大鼠图谱在立体定向仪下以(AP:-2.6 mm,ML:±0.6 mm,DV:-9.6 mm)为坐标,1.5 mA电流持续通电25 s,损毁SD大鼠的双侧脑腹内侧核(ventromedial hypothalamus,VMH)和弓状核(arcuate nucleus,ARC)。实验期间规律记录两组大鼠的体质量、摄食饮水量,术后28 d处死大鼠,检测肾周脂肪质量变化、体长距离,HE染色检测肝脏、脂肪组织变化情况,ELISA法测定血清瘦素含量,Western blot检测下丘脑瘦素受体(leptin receptor,LEPR)表达。结果:(1)与对照组相比较,术后28 d模型组大鼠体质量[(427.5±17.7)g]、体质量增长[(208.5±14.8)g]较对照组体质量[(349.2±17.7)g]、体质量增长[(136.2±21.4)g]显著增加(t=7.661、6.806,均P<0.001)。(2)术后28 d模型组大鼠日摄食量[(44.2±6.6)g]较对照组大鼠[(23.0±3.6)g]显著增加(t=6.918,P<0.001),但模型组大鼠日饮水量[(37.5±12.1)ml]与对照组[(35.0±11.8)ml]比较,差异无统计学意义(t=0.361,P=0.726)。(3)术后28 d模型组大鼠肾周脂肪质量[(13.4±2.7)g]较对照组大鼠[(6.3±0.9)g]增加(t=4.250,P<0.05),模型组大鼠体长[(21.8±0.4)cm]较对照组大鼠[(23.4±0.2)cm]减少(t=-6.788,P<0.01),模型组大鼠Lee指数(348.9±8.5)较对照组大鼠(305.5±4.3)显著增加(t=7.898,P<0.01)。(4)术后28 d模型组大鼠血清瘦素含量[(8324.10±159.00)μg/L]较对照组大鼠[(2705.31±407.10)μg/L]显著增加(t=25.712,P<0.001),模型组大鼠下丘脑外侧区(lateral hypothalamus area,LHA)LEPR蛋白表达量(1.3±0.1)较对照组大鼠(0.9±0.1)显著增加(t=4.932,P<0.01)。结论:两点法电损毁SD大鼠的双侧VMH和ARC可构建下丘脑性肥胖大鼠模型。Objective:To construct a rat model of hypothalamic obesity by two point electrical damage to the ventromedial hypothalamus and arcuate nucleus.Methods:Twenty adult male SD rats of SPF grade were randomly divided into experimental group and sham operation group.A 25GA(0.45 mm)solid iron needle was used,the needle was coated with an insulating layer,and the tip exposed a 0.5 mm conductive area.With reference to The Rat Brain in Stereotaxic Coordinates and using the stereotactic instrument(AP:-2.6 mm,ML:±0.6 mm,DV:-9.6 mm)as the coordinate,1.5 mA current was continuously applied for 25 s,the ventromedial nucleus(VMH)and arcuate nucleus(ARC)of bilateral brain in SD rats was damaged.During the experiment,the body weight(BW),food intake(FI)and water intake(WI)of the two groups were recorded regularly.The rats were sacrificed on the 28th day after the operation,and the changes of periprenal fat mass and body length were measured.The changes of liver and adipose tissue were detected by HE staining method,leptin by ELISA,leptin receptor(LEPR)by Western blot.Results:(1)The body weight of rats in the experimental group((427.5±17.7)g)and weight gain((208.5±14.8)g)were significantly increased compared with the rats in the control group((349.2±17.7)g),((136.2±21.4)g)on the 28th day after operation(t=7.661,6.806,both P<0.001).(2)The daily food intake of rats in the experimental group((44.2±6.6)g)on the 28th day after surgery was significantly higher than that in the control group((23.0±3.6)g)(t=6.918,P<0.001).There was no significant difference of the daily drinking water of rats between experimental group((37.5±12.1)ml)and the control group((35.0±11.8)ml)(t=0.361,P=0.726).(3)Perikidney fat mass of experimental group rats((13.4±2.7)g)significantly increased 28 days after operation compared with control group rats((6.3±0.9)g)(t=4.250,P<0.05).The naso-anal length of experimental group((21.8±0.4)cm)was significantly decreased compared with the control group((23.4±0.2)cm)(t=-6.788,P<0.01).The Lee index of the experimen

关 键 词：下丘脑 电损毁 肥胖 动物模型 瘦素抵抗 大鼠 

分 类 号：R-332[医药卫生]