LncRNA LUCAT1调控miR-375/HMGB1轴对多囊卵巢综合征大鼠胰岛素抵抗的机制研究  

The Mechanism of LncRNA LUCAT1 Regulating miR-375/HMGB1 Axis on Insulin Resistance in Polycystic Ovarian Syndrome Rats

作　　者：潘静[1] 热汗古丽·库尔班[1] 吐松古·艾买尔 沈娟娟[1] 薄晓莉[1] PAN Jing;Rehanguli·Kurban;Tusonggu·Aimar;SHEN Juan-juan;BO Xiao-li(Gynecology,the Second Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,830063,China)

机构地区：[1]新疆医科大学第二附属医院妇科,新疆乌鲁木齐830063

出　　处：《现代生物医学进展》2024年第8期1439-1443,共5页Progress in Modern Biomedicine

基　　金：新疆维吾尔自治区自然科学基金项目(2022D01C496)。

摘　　要：目的:研究长链非编码RNA(LncRNA)LUCAT1调控miR-375/高迁移率族蛋白-1(HMGB1)轴对多囊卵巢综合征(PCOS)大鼠胰岛素抵抗的相关分子机制,为疾病的临床干预提供新靶点。方法:选择SD雌性大鼠3周龄(平均体重50 g)20只,随机分为对照组和模型组各10只,模型组采用皮下注射脱氢表雄酮(DHEA)的方法复制PCOS模型。qRT-PCR法检测卵巢组织LncRNA LUCAT1和miR-375表达量,Western blot法检测HMGB1蛋白,常规生化法检测血清空腹血糖(FBG)和空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)。随后分离卵巢颗粒细胞(GCs)并采用免疫荧光法检测卵泡刺激素受体(FSHR)进行细胞鉴定。体外构建si-LUCAT1和si-NC并转染GCs,培养48h后检测LUCAT1、miR-375和HMGB1表达量。结果:与对照组大鼠相比,模型组卵巢组织LncRNA LUCAT1和HMGB1蛋白表达量显著升高,而miR-375表达量显著下降(P<0.05);血清FBG和FINS水平以及HOMA-IR值明显升高(P<0.05)。与si-NC组GCs细胞相比,si-LUCAT1组LUCAT1和HMGB1表达量显著下降,而miR-375表达量增加(P<0.05)。结论:LncRNA LUCAT1可能通过调控miR-375/HMGB1轴并参与PCOS的发生以及胰岛素抵抗。Objective:To investigate the molecular mechanism of long-chain non-coding RNA(LncRNA)LUCAT1 regulating miR-375/high mobility group protein-1(HMGB1)axis on insulin resistance in polycystic ovary syndrome(PCOS)rats,so as to provide new targets for clinical intervention of disease.Methods:Twenty 3-week-old(average weight 50 g)female SD rats were selected and randomly divided into control group and model group,with 10 rats in each group.The model group replicated PCOS model by subcutaneous injection of dehydroepiandrosterone(DHEA).qRT-PCR was used to detect the expression levels of LncRNA LUCAT1 and miR-375 in ovarian tissues,Western blot was used to detect HMGB1 protein,routine biochemical methods were used to detect serum fasting blood glucose(FBG)and fasting insulin(FINS),and insulin resistance index(HOMA-IR)was calculated.Subsequently,ovarian granulosa cells(GCs)were isolated and immunofluorescence was used to detect follicle stimulating hormone receptors(FSHR)for cell identification.Si-LUCAT1 and si-NC in vitro were constructed then transfected into GCs.After 48 hours of cultivation,the expression levels of LUCAT1,miR-375,and HMGB1 were detected.Results:Compared with the control group of rats,the expression levels of LncRNA LUCAT1 and HMGB1 protein in the ovarian tissues of the model group were significantly higher,while the expression level of miR-375 was significantly lower(P<0.05);the levels of serum FBG and FINS,as well as HOMA-IR value,were significantly higher,too(P<0.05).Compared with the si-NC group of GCs cells,the expression levels of LUCAT1 and HMGB1 in the si-LUCAT1 group were significantly less,while the expression level of miR-375 was more,too(P<0.05).Conclusion:LncRNA LUCAT1 may participate in the occurrence of PCOS and insulin resistance by regulating the biological functions of miR-375/HMGB1 axis.

关 键 词：多囊卵巢综合征 胰岛素抵抗 长链非编码RNA LUCAT1 miR-375 高迁移率族蛋白-1 

分 类 号：R-33[医药卫生] R711.75