基于NLRP3/Caspase-1/GSDMD信号通路探讨姜黄素对过氧化氢诱导的子宫内膜上皮细胞焦亡的影响OA
Effects of Curcumin on Hydrogen Peroxide-induced Pyroptosis of Endome-trial Epithelial Cells Through NLRP3/Caspase-1/GSDMD Signaling Pathway
目的:分析姜黄素对过氧化氢(H2O2)诱导的子宫内膜上皮细胞焦亡、促炎因子的释放及Nod 样受体蛋白3(NLRP3)/半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)/消皮素 D(GSDMD)通路的活性变化,探讨姜黄素保护子宫内膜上皮细胞的作用机制.方法:获取原代人的子宫内膜上皮细胞,分成4组:正常组、姜黄素组、H2O2 组和姜黄素治疗组.Hoechst/PI荧光染色法观察细胞形态变化;CCK-8 法测定细胞活力;乳酸脱氢酶(LDH)试剂盒测定细胞LDH释放率;酶联免疫吸附试验测定细胞白介素-1β(IL-1β)和白介素-18(IL-18)的分泌量;Western Blot 分析 NLRP3、Caspase-1、剪切的Caspase-1(cleaved Caspase-1)、GSDMD及消皮素 D蛋白的N端片段(GSDMD-N)的蛋白表达.结果:正常组和姜黄素组相比各指标差异均无统计学意义(P>0.05);和正常组相比,H2O2 组的细胞活力降低(P<0.05),LDH 释放率升高(P<0.05),IL-1β和IL-18分泌量均增加(P<0.05),NLRP3、cleaved Caspase-1/Caspase-1及GSDMD-N/GSDMD值均升高(P<0.05);和H2O2 组相比,姜黄素治疗组的细胞活力增高(P<0.05),LDH 释放率降低(P<0.05),IL-1β和IL-18分泌量均减少(均P<0.05),NLRP3、cleaved Caspase-1/Caspase-1及GSDMD-N/GSDMD值均下降(均P<0.05).结论:姜黄素可能通过调控NLRP3/Caspase-1/GSDMD信号通路,减轻过氧化氢诱导的子宫内膜上皮细胞焦亡和促炎因子的释放,进而对子宫内膜发挥保护效应.
Objective:To analyze the effects of curcumin on hydrogen peroxide(H2O2)-induced pyroptosis,pro-inflammatory factor release,and the activity of NLRP3/Caspase-1/GSDMD signaling pathway in endometrial epithelial cells,and to explore the potential mechanism of curcumin in protecting endometrial epithelial cells.Methods:Primary human endometrial epithelial cells were isolated and collected,then randomly divided into four groups:normal group,curcumin group,H2O2 model group,and curcumin treatment group.Hoechst/PI fluorescence staining was performed to observe cellular morphological changes,CCK-8 assay to detect the cell viability,LDH detection kit to measure the LDH release rate,Enzymelinked immunosorbent assay(ELISA)to detect the secretion levels of interleukin1β(IL-1β)and interleukin18(IL-18),and Western Blot to analyze the protein expression of NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,and the Nterminal fragment of GSDMD(GSDMD-N).Results:There were no significant differences in all detected indicators between the normal group and the curcumin group(P>0.05).Compared with the normal group,the H2O2 group exhibited significantly decreased cell viability,increased LDH release rate,and elevated secretion levels of IL-1β and IL-18(all P<0.05).Meanwhile,the protein expression levels of NLRP3 and the ratios of cleaved Caspase-1/Caspase-1 and GSDMD-N/GSDMD were significantly upregulated in the H2O2 group(P<0.05).Compared with the H2O2 group,the curcumin treatment group showed significantly increased cell viability,reduced LDH release rate,and decreased secretion of IL-1β and IL-18(all P<0.05).Moreover,curcumin intervention significantly downregulated the expression of NLRP3 and decreased the ratios of cleaved Caspase-1/Caspase-1 and GSDMD-N/GSDMD(all P<0.05).Conclusion:Curcumin may alleviate H2O2-induced pyroptosis and the release of pro-inflammatory factors in endometrial epithelial cells by regulating the NLRP3/Caspase-1/GSDMD signaling pathway,thereby exerting a protective effect on endometrium.
宋利华;栗志英;马景红;贾晓楠;冯文娇;单铁英;李俊娇
河北工程大学附属医院,河北 邯郸 056002河北工程大学附属医院,河北 邯郸 056002河北工程大学附属医院,河北 邯郸 056002邯郸市第一医院,河北 邯郸 056002邯郸市第一医院,河北 邯郸 056002河北工程大学医学院,河北 邯郸 056038河北工程大学附属医院,河北 邯郸 056002
医药卫生
姜黄素过氧化氢子宫内膜上皮细胞焦亡促炎因子NLRP3/Caspase-1/GSDMD通路子宫内膜异位症
CurcuminH2O2endometrial epithelial cellspyroptosispro-inflammatory factorsNLRP3/Caspase-1/GSDMD pathwayendometriosis
《河北中医药学报》 2026 (3)
9-14,6
河北省自然科学基金资助项目(H2021402003)河北省医学科学研究课题计划资助(20250164)
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