TXNIP在妊娠糖尿病胎盘滋养层脂质沉积中的作用  

Role of TXNIP in lipid deposition of placental trophoblast in gestational diabetes mellitus

作　　者：杨洁 贾剑超 张英 萨日娜 李东芳 李治颖 黄娜 俞兰 Yang Jie;Jia Jianchao;Zhang Ying;Sa Rina;Li Dongfang;Li Zhiying;Huang Na;Yu Lan(Clinical Medical Research Center/Inner Mongolia Key Laboratory of Gene Regulation of the Metabolic Disease,Inner Mongolia People’s Hospital/Basic Research Institute of Inner Mongolia Academy of Medical Sciences,Hohhot 010017,China)

机构地区：[1]内蒙古自治区人民医院临床医学研究中心/内蒙古自治区代谢紊乱疾病基因调控重点实验室/内蒙古医学科学院基础研究所,呼和浩特010017

出　　处：《临床与实验病理学杂志》2025年第4期483-490,共8页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金(82160299);内蒙古自治区自然科学基金(2024QN08015);内蒙古自治区科技计划项目(2020GG0116);内蒙古医学科学院公立医院科研联合基金科技项目(2023GLLH0090)。

摘　　要：目的探讨硫氧还蛋白结合蛋白(thioredoxin-interacting protein,TXNIP)在妊娠糖尿病(gestational diabetes mellitus,GDM)患者胎盘组织中的表达及其在胎盘滋养层脂质沉积中的作用。方法收集16例GDM产妇和25例正常糖耐量(normal glucose tolerance,NGT)产妇的胎盘组织,同时建立高糖诱导人绒毛膜滋养层细胞(HTR-8/SVneo)体外模型,分为正常糖对照组(NG)、高糖组(HG)、高糖+si无义干扰组(HG+siNC)和高糖+TXNIP siRNA组(HG+siTXNIP),采用HE染色观察胎盘组织病理结构与形态变化,油红O染色检测组织和细胞脂滴积累情况,免疫细胞化学法检测细胞中TXNIP的表达及定位,实时荧光定量PCR与免疫印记法检测TXNIP与脂肪生成蛋白SREBP1 mRNA与蛋白表达水平,分析高糖诱导下TXNIP的表达与脂滴积累的关系。结果高糖导致GDM胎盘结构异常,表现为GDM组胎盘的人绒毛膜绒毛间质组织所占面积减少,胎儿毛细血管大小不一、管腔扩张;与NGT组相比,GDM胎盘组织脂滴积累增加,TXNIP mRNA与蛋白表达增加(P<0.05);在高糖诱导的HTR-8/SVneo细胞中,脂滴形成增加,TXNIP和SREBP1表达上调(P<0.05);TXNIP siRNA转染逆转了高糖诱导的基因表达水平和脂质沉积情况(P<0.05)。结论TXNIP参与了GDM胎盘滋养层异常的脂质沉积过程。Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The placenta tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Meanwhile,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense interference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation induced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P<0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P<0.05).On the contrary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P<0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

关 键 词：妊娠糖尿病 硫氧还蛋白结合蛋白 胎盘滋养层 脂质 

分 类 号：R714.25[医药卫生—妇产科学]