姜黄素对AngⅡ诱导的子宫内膜上皮细胞转分化及AKT/GSK-3β/β-catenin通路激活的影响

职业与健康 ›› 2025, Vol. 41 ›› Issue (4): 458-462.

姜黄素对AngⅡ诱导的子宫内膜上皮细胞转分化及AKT/GSK-3β/β-catenin通路激活的影响

董静¹, 宋利华², 董永杰^3a, 栗志英², 宋玉杰^3b, 李玲^3b

1.邯郸市疾病预防控制中心微生物检验科,河北邯郸 056002;
2.河北工程大学附属医院心血管内科,河北邯郸 056002;
3.邯郸市中心医院a 普外科b妇科,河北邯郸 056002

收稿日期:2024-06-17 修回日期:2024-07-08 出版日期:2025-02-15 发布日期:2025-12-12
通信作者: 宋玉杰,副主任医师,E-mail：zxw071009@163.com
作者简介:董静,女,副主任技师,主要从事微生物检验工作。
基金资助:
邯郸市科学技术研究与发展计划项目（23422083199）

Effect of curcumin on endometrial epithelial cells transdifferentiation and activation of AKT/GSK-3β/β-catenin pathway induced by AngⅡ

DONG Jing¹, SONG Lihua², DONG Yongjie^3a, LI Zhiying², SONG Yujie^3b, LI Ling^3b

1. Microbial Laboratory Department,Handan Center for Disease Control and Prevention,Handan,Hebei 056002,China;
2. Department of Cardiovascular Medicine Department,Affiliated Hospital of Hebei Engineering University,Handan,Hebei 056002,China;
3. a Department of General Surgery,b Department of Gynecology,Handan Central Hospital,Handan,Hebei 056002,China

Received:2024-06-17 Revised:2024-07-08 Online:2025-02-15 Published:2025-12-12
Contact: SONG Yujie,Associate chief physician,E-mail：zxw071009@163.com

摘要/Abstract

摘要： 目的研究姜黄素对血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）诱导的子宫内膜上皮细胞（endometrial epithelial cells,EECs）增殖、分泌、转分化能力及激活蛋白激酶B（protein kinase B,AKT）/糖原合成酶激酶-3β（glycogen synthase kinase-3β,GSK-3β）/β-连环蛋白（β-catenin）通路的变化,探讨姜黄素对子宫内膜纤维化的保护机制。方法分离并鉴定原代人EECs,依据处理方式不同将其分成正常组、姜黄素组、AngⅡ组及姜黄素治疗组4组。正常组：常规孵育液;姜黄素组：含有姜黄素（30μmol/L）的孵育液;AngⅡ组：含有AngⅡ（10^-6 mol/L）的孵育液;姜黄素治疗组：含有AngⅡ（10^-6 mol/L）和姜黄素（30 μmol/L）的孵育液,各组处理时间均为48 h。比较各组细胞的增殖情况;分析细胞孵育液中Ⅰ、III型胶原蛋白的分泌量、Western blot 检测细胞转分化标志分子钙黏蛋白E（E-cadherin,E-cad）和α-平滑肌肌动蛋白（alpha smooth muscle Actin,α-SMA）;AKT/GSK-3β/β-catenin通路分子磷酸化蛋白激酶B（phosphorylated protein kinase B,p-AKT）、磷酸化糖原合成酶激酶-3β（phosphorylated glycogen synthase kinase-3β,p-GSK-3β）和β-catenin的表达水平。结果 DHA组和正常组相比,细胞增殖、孵育液中Ⅰ、III型胶原分泌量、转分化分子以及AKT/GSK-3β/β-catenin通路分子的表达水平差异均无统计学意义（均P>0.05）。AngⅡ组和正常组相比,细胞量（0.122±0.002）增多、Ⅰ型胶原[（0.538±0.093）ng/L]和III型胶原[（0.492±0.097）ng/L]分泌量上升、转分化标志分子a-SMA（0.492±0.031）、AKT/GSK-3β/β-catenin通路分子p-AKT（1.119±0.064）、p-GSK-3β（0.904±0.057）和β-catenin（0.121±0.002）表达水平均升高（均P<0.05）,而E-cad（0.349±0.021）表达水平下降（P<0.05）。姜黄素治疗组和AngⅡ组相比,细胞量（0.118±0.001）减少、Ⅰ型胶原[（0.348±0.063）ng/L]和III型胶原[（0.306±0.063）ng/L]分泌量下降、转分化标志分子a-SMA（0.221±0.015）、AKT/GSK-3β/β-catenin通路分子p-AKT（0.705±0.052）、p-GSK-3β（0.563±0.029）和β-catenin（1.106±0.070）表达水平均降低（均P<0.05）,而E-cad（0.661±0.024）表达水平升高（P<0.05）。结论姜黄素能调节AKT/GSK-3β/β-catenin通路抑制AngⅡ诱导的子宫内膜上皮细胞增殖、分泌及转分化能力。

关键词: 姜黄素, 血管紧张素Ⅱ, 子宫内膜上皮细胞, 转分化, AKT/GSK-3β/β-catenin通路

Abstract: Objective To analyze the effects of curcumin on the proliferation,secretion,transdifferentiation ability,and activation ofprotein kinase B（AKT）/glycogen synthase kinase-3β（GSK-3β）/β-catenin pathway in endometrial epithelial cells（EECs） induced by angiotensinⅡ（Ang Ⅱ）,and exploring the protective mechanism of curcumin on endometrial fibrosis. Methods Primary human EECs were separated and identified,and were divided into four groups based on different treatment methods：normal group,curcumin group,AngⅡgroup,and curcumin treatment group.Normal group：conventional incubation solution,curcumin group：incubation solution containing curcumin（30 μmol/L）,AngⅡ group：incubation solution containing AngⅡ（10^-6 mol/L）,curcumin treatment group：incubation solution containing AngⅡ（10^-6 mol/L） and curcumin（30 μmol/L）,each group was treated for 48 hours.The proliferation status of each group of cells was compared,and the secretion levels of type I and Ⅲ collagen in the cell culture medium were analyzed. Western blot was used to detect the protein expression level such as cell differentiation marker molecules E-cadherin and alpha smooth muscle actin（α-SMA）,AKT/GSK-3β/β-Catenin pathway molecules phosphorylated protein kinase B（p-AKT）,phosphorylated glycogen synthase kinase-3β（p-GSK-3β） and β-catenin. Results There were no statistically significant differences in cell proliferation,secretion of typeⅠand Ⅲ collagen in the incubation solution,expression levels of transdifferentiation molecules,and AKT/GSK-3β/β-catenin pathway molecules between the DHA group and the normal group（all P>0.05）.Compared with the normal group,the AngⅡgroup showed an increase in cell number（0.122±0.002）,secretion of type I collagen（0.538±0.093） and typeⅢcollagen（0.492±0.097）,as well as an increase in the expression level of transdifferen tiation marker molecules a-SMA（0.492±0.031）,AKT/GSK-3β/β-catenin pathway molecules p-AKT（1.119±0.064）,p-GSK-3β（0.904±0.057）,and β-catenin（0.121±0.002）（all P<0.05）,while the expression level of E-Cad（0.349±0.021） decreased（P<0.05）.Compared with the AngⅡ group,the curcumin treatment group showed a decrease in cell number（0.118±0.001）,a decreased in secretion of type I collagen（0.348±0.063） and typeⅢcollagen（0.306±0.063）,a decrease in the expression level of transdifferentiationmarker molecules a-SMA（0.221±0.015）,AKT/GSK-3β/β-catenin pathway molecules p-AKT（0.705±0.052）,p-GSK-3β（0.563±0.029）,and β-catenin（1.106±0.070）（all P<0.05）,while the expression level of E-Cad（0.661±0.024） increased（P<0.05）. Conclusion Curcumin can regulate AKT/GSK-3β/β-catenin pathway and inhibit EECs proliferation,secretion,and transdifferentiation induced by AngⅡ.

Key words: Curcumin, Angiotensin Ⅱ, Endometrial epithelial cells, Transdifferentiation, AKT/GSK-3β/β-catenin pathway

董静, 宋利华, 董永杰, 栗志英, 宋玉杰, 李玲. 姜黄素对AngⅡ诱导的子宫内膜上皮细胞转分化及AKT/GSK-3β/β-catenin通路激活的影响. [J]职业与健康, 2025, 41(4): 458-462.

DONG Jing, SONG Lihua, DONG Yongjie, LI Zhiying, SONG Yujie, LI Ling. Effect of curcumin on endometrial epithelial cells transdifferentiation and activation of AKT/GSK-3β/β-catenin pathway induced by AngⅡ. [J]OCCUPATION AND HEALTH, 2025, 41(4): 458-462.

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