高糖通过激活NLRP3炎症小体促进胎盘滋养细胞IL-1β、IL-18的释放

High glucose promotes the release of IL-1βand IL-18 from placental trophoblast by activating NLRP3 inflammasome

目的研究高糖通过激活NLRP3炎症小体对胎盘滋养细胞白细胞介素(IL)-1β和IL-18分泌的影响。方法收集妊娠期糖尿病(GDM)胎盘和对照胎盘,检测NLRP3、含半胱氨酸的天冬氨酸蛋白水解酶-1(Caspase-1)的表达水平。培养人胎盘滋养层细胞HTR-8/SVneo,分为对照组(5.5 mmol/L葡萄糖)、高糖组(25mmol/L葡萄糖)、对照溶剂二甲基亚砜(DMSO)+高糖组、NLRP3炎症小体抑制剂Ac-YVAD-cmk+高糖组,检测细胞中NLRP3、Caspase-1的表达水平及培液中IL-1β和IL-18的含量。结果GDM胎盘中NLRP3、Caspase-1的表达水平高于正常胎盘(P<0.05),且与HOMA-IR、空腹胰岛素呈正相关;高糖组HTR-8/SVneo细胞NLRP3、Caspase-1的表达水平及IL-1β、IL-18的分泌水平高于对照组(P<0.05);Ac-YVAD-cmk明显降低高糖刺激的IL-1β、IL-18分泌(P<0.05)。结论高糖通过激活NLRP3炎症小体促进胎盘滋养细胞IL-1β、IL-18的释放。

Objective To investigate the effect of high glucose on the release of interleukin(IL)-1βand IL-18 in placental trophoblast by activating NLRP3 inflammasome.Methods Gestational diabetes mellitus(GDM)placentas and control placentas were collected and the expression levels of NLRP3 and Caspase-1 were determined.Human placental trophoblast HTR-8/SVneo were cultured and divided into control group(5.5 mmol/L glucose),high glucose group(25 mmol/L glucose),DMSO+high glucose group,and Ac-YVAD-cmk(NLRP3 inflammasome inhibitor)+high glucose group.The expression levels of NLRP3 and Caspase-1 in cells as well as the contents of IL-1βand IL-18 in the medium were determined.Results The expression levels of NLRP3 and Caspase-1 in GDM placenta were higher than those in control placenta(P<0.05)and positively correlated with homeostasis model assessment of insulin resistant index(HOMA-IR)and fasting insulin.The expression levels of NLRP3 and Caspase-1 in HTR-8/SVneo cells and the secretion levels of IL-1βand IL-18 in high glucose group were higher than those in control group(P<0.05).Ac-YVAD-cmk significantly suppressed high glucose-stimulated IL-1βand IL-18 secretion(P<0.05).Conclusion High glucose promotes the release of IL-1βand IL-18 from placental trophoblast via activating NLRP3 inflammasome.