miR⁃27a靶向调节TLR4减轻糖尿病妊娠大鼠氧化应激和炎症损伤  

miR⁃27a attenuates oxidative stress and inflammatory damage in diabetic pregnant rats by targeting TLR4

作　　者：张翠翠[1] 孙文萍[1] 谢玲[1] ZHANG Cuicui;SUN Wenping;XIE Ling(Department of Obstetrics and Gynecology,Qinghai Red Cross Hospital,Xining 810099,China)

机构地区：[1]青海红十字医院产一科,西宁810099

出　　处：《实用医学杂志》2023年第12期1487-1493,共7页The Journal of Practical Medicine

基　　金：青海省科技项目(编号:2016⁃SF⁃127)。

摘　　要：目的探讨MicroRNA⁃27a(miR⁃27a)在妊娠期糖尿病(GDM)大鼠胎盘组织中的表达及其对GDM大鼠氧化应激和炎症的影响,并分析潜在机制。方法SD正常妊娠大鼠腹腔注射链脲佐菌素(STZ)诱导建立GDM模型,造模成功后分为模型组(model组)、agomir⁃NC组、miR⁃27a agomir组、miR⁃27a agomir+脂多糖(LPS)组,每组12只;另取12只正常妊娠大鼠为对照组(control组)。检测大鼠空腹血糖(FBG)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA⁃IR);分析妊娠结局和胎盘质量;检测胎盘组织白细胞介素⁃1β(IL⁃1β)、肿瘤坏死因子⁃α(TNF⁃α)水平和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性以及丙二醛(MDA)含量;苏木精⁃伊红(HE)染色、TUNEL法检测胰腺和胎盘组织损伤及细胞凋亡情况;实时定量PCR(RT⁃qPCR)、Western blot检测胎盘组织miR⁃27a与Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子⁃κB p65(NF⁃κB p65)的mRNA和蛋白水平。结果miR⁃27a的过表达显著降低了GDM大鼠FBG、FINS和HOMA⁃IR,并伴随着促炎细胞因子水平和氧化应激的降低,改善了胎盘和胰腺组织损伤和细胞凋亡及妊娠结局,并抑制了胎盘中TLR4/MyD88/NF⁃κB信号通路的激活(P<0.05)。结论miR⁃27a过表达可减轻GDM大鼠胎盘炎症反应和氧化应激,减轻IR,其作用机制可能与抑制TLR4/MyD88/NF⁃κB信号通路激活有关。Objective To investigate the expression of MicroRNA⁃27a(miR⁃27a)in the placenta of gesta⁃tional diabetes mellitus(GDM)rats and its effects on oxidative stress and inflammation in GDM rats,as well as to analyze the underlying mechanism.Methods SD normal pregnant rats were injected intraperitoneally with strepto⁃zotocin(STZ)to induce the establishment of GDM models.After successful modeling,they were divided into four groups:model group,agomir⁃NC group,miR⁃27a agomir group,and miR⁃27a agomir+lipopolysaccharide(LPS)group,eachwith 12 rats;the control group consisted of12 normal pregnant rats.The levels of fasting blood glucose(FBG)and fasting insulin(FINS)in rats were detected,and the insulin resistance index(HOMA⁃IR)was calculated;the pregnancy outcome and placenta quality were analyzed;the levels of interleukin 1β(IL⁃1β)and tumor necrosis factorα(TNF⁃α),the activities of superoxide dismutase(SOD)and catalase(CAT),and the content of malondialde⁃hyde(MDA)in placenta tissuewere determined;Hematoxylin⁃Eosin(HE)staining and TUNEL method were used to detect pancreatic and placental tissue damage and cell apoptosis;and real⁃time quantitative PCR(RT⁃qPCR)and Western blot were used to detect the levels of miR⁃27a,Toll⁃like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor⁃κB p65(NF⁃κB p65)mRNAs and proteins in placental tissues.Results Overexpression of miR⁃27a significantly reduced FBG,FINS and HOMA⁃IR in GDM rats,accompanied by a reduction in pro⁃inflam⁃matory cytokine levels and oxidative stress,improved placental and pancreatic tissue damage and apoptosis,and the pregnancy outcome,and inhibited the activation of the TLR4/MyD88/NF⁃κB signaling pathway in the placenta(P<0.05).Conclusion The overexpression of miR⁃27a can reduce the placental inflammation,oxidative stress,and IRin GDM rats.Its mechanism could be related to the inhibition of the TLR4/MyD88/NF⁃κB signaling pathway.

关 键 词：MicroRNA⁃27a 妊娠期糖尿病 炎症反应 氧化应激 胰岛素抵抗 Toll样受体4 髓样分化因子88 核因子⁃κB 

分 类 号：R285.5[医药卫生—中药学]