高脂饮食对甲状腺生物钟基因Bmal1敲除小鼠甲状腺形态和功能及糖脂代谢的影响  

Effects of high-fat diet on the morphology and function of the thyroid gland and glycolipid metabolism in thyroid clock gene Bmal1 knockout mice

作　　者：叶绮婷 张诗丽 冯雯雯 关海霞 Ye Qiting;Zhang Shili;Feng Wenwen;Guan Haixia(Department of Endocrinology,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China)

机构地区：[1]南方医科大学附属广东省人民医院、广东省医学科学院内分泌科,广州510080

出　　处：《中华医学杂志》2025年第5期371-378,共8页National Medical Journal of China

基　　金：国家自然科学基金(82170803)。

摘　　要：目的探究高脂饮食(HFD)喂养后甲状腺生物钟基因Bmal1敲除后小鼠甲状腺形态和功能发生的变化,并分析其对小鼠糖脂代谢的影响。方法构建甲状腺生物钟基因Bmal1特异性敲除小鼠(T-Bmal1^(-/-))模型(敲除组,n=10),并以无甲状腺过氧化物酶-环化重组酶的Bmal1^(flox/flox)小鼠(T-Bmal1^(+/+))作为对照组(未敲除组,n=10)。喂养至6周(体重20~23 g),应用随机数字表法将敲除组和未敲除组小鼠平均分为2组,分别给予普通饮食(ND)或HFD喂养,即最终分为ND未敲除组、HFD未敲除组、ND敲除组和HFD敲除组,每组5只。自第6周起连续10周测量小鼠体重,第14周第1天行腹腔注射葡萄糖耐量试验(IPGTT),第15周第1天行腹腔注射胰岛素耐量试验(IPITT),小鼠出生第16周第1天分别在7点、13点、19点及次日1点麻醉后取眼球血0.2 ml,最后取甲状腺、肝脏、肾脏、脾脏、腹股沟白色脂肪和肩胛骨棕色脂肪。检测比较各组甲状腺组织形态、甲状腺功能指标、甲状腺中生物钟基因和甲状腺激素合成和分泌相关基因表达情况,以及体重、IPGTT和IPITT曲线下面积(AUC)和血脂水平。结果ND敲除组和ND未敲除组小鼠甲状腺滤泡个数、甲状腺滤泡面积、甲状腺滤泡腔高度差异均无统计学意义(均P>0.05),但HFD敲除组的甲状腺滤泡腔高度小于HFD未敲除组[(25.8±1.6)比(54.4±9.5)μm,P=0.002]。ND或HFD喂养后敲除组血清T4水平均高于未敲除组(均P<0.05)。ND敲除组与ND未敲除组钠碘转运体mRNA表达水平差异无统计学意义(P=0.550),但HFD敲除组钠碘转运体mRNA表达水平高于HFD未敲除组[0.67±0.27比0.20±0.09,P=0.006]。ND敲除组和ND未敲除组体重增长和腹股沟白色脂肪重量差异均无统计学意义(均P>0.05),但HFD敲除组体重增长和腹股沟白色脂肪组织重量均低于HFD未敲除组(均P<0.05)。IPGTT提示,ND敲除组和ND未敲除组的AUC差异无统计学意义(P=0.226),而HFD敲除组AUC小于HFD未敲Objective:To investigate the changes in thyroid morphology and function in mice with thyroid-specific knockout of the clock gene Bmal1 under high-fat diet(HFD),and to examine its effects on glycolipid metabolism in mice.Methods:Construct a mouse model with specific knockout of the Bmal1 gene in the thyroid(T-Bmal1^(-/-))(knockout group,n=10),and use Bmal1^(flox/flox) mice without thyroid peroxidase-cyclization recombination enzyme(T-Bmal1^(+/+))as the control group(non-knockout group,n=10).The mice were fed until 6 weeks(body weight 20-23 g),and then use the random number table method to evenly divide each group of mice into two subgroups.They were then fed either with normal diet(ND)or(HFD),resulting in four final groups:ND non-knockout group,HFD non-knockout group,ND knockout group,and HFD knockout group,with 5 mice in each group.From the 6th week onwards,the body weights of the mice were measured for 10 consecutive weeks.On the first day of the 14th week,the intraperitoneal glucose tolerance test(IPGTT)was conducted,and on the first day of the 15th week,the intraperitoneal insulin tolerance test(IPITT)was performed.On the first day of the 16th week after the mice were born,blood samples(0.2 ml)were taken from the eyes under anesthesia at 7∶00,13:00,19:00,and 1∶00 the next day,and the thyroid,liver,kidneys,spleen,inguinal white adipose tissue,and scapular brown adipose tissue were rapidly removed.Thyroid tissue morphology,thyroid function indexes,thyroid clock genes and thyroid hormone synthesis and secretion related genes expression,body weight,IPGTT and IPITT area under the curve(AUC)and lipid levels were detected and compared among all groups.Results:There was no significant difference in the number of thyroid follicles,the area of thyroid follicles and the height of thyroid follicle cavity between ND knockout group and ND non-knockout group(all P>0.05),but the height of thyroid follicle cavity in HFD knockout group was lower than that in HFD knockout group[(25.8±1.6)vs(54.4±9.5)μm,P=0.002].The level

关 键 词：小鼠 基因敲除 甲状腺 BMAL1 生物钟 糖脂代谢 

分 类 号：R581[医药卫生—内分泌]