双氢青蒿素通过调节自噬拮抗血管紧张素Ⅱ诱导的子宫内膜上皮细胞转分化  

Dihydroartemisinin Antagonizes AngⅡ-Induced Transdifferentiation of Endometrial Epithelial Cells by Regulating Autophagy

作　　者：李玲 宋玉杰 潘云[3] 秦燕 耿晓 单铁英[4] LI Ling;SONG Yujie;PAN Yun;QIN Yan;GENG Xiao;SHAN Tieying(Physical Examination Center,Handan Central Hospital,Handan,Hebei 056002,China;Gynecology Department,Handan Central Hospital,Handan,Hebei 056002,China;Department of Intensive Care Medicine,Handan Central Hospital,Handan,Hebei 056002,China;School of Medicine,Hebei University of Engineering,Handan,Hebei 056038,China)

机构地区：[1]河北省邯郸市中心医院体检中心,河北邯郸056002 [2]河北省邯郸市中心医院妇科,河北邯郸056002 [3]河北省邯郸市中心医院重症医学科,河北邯郸056002 [4]河北工程大学医学院,河北邯郸056038

出　　处：《转化医学杂志》2024年第10期1733-1737,1752,共6页Translational Medicine Journal

基　　金：邯郸市科学技术研究与发展计划项目(23422083199)。

摘　　要：目的研究双氢青蒿素对血管紧张素Ⅱ(AngⅡ)诱导的子宫内膜上皮细胞(EECs)转分化及自噬蛋白表达的影响,探讨双氢青蒿素拮抗子宫内膜纤维化的作用机制。方法获取人原代EECs,分组为正常对照组、AngⅡ组、双氢青蒿素组及雷帕霉素组。正常对照组干预方法为细胞孵育液,AngⅡ组为细胞孵育液+10^(-6)mol/L AngⅡ,双氢青蒿素组为细胞孵育液+10-6mol/LAngⅡ+100 ng/mL双氢青蒿素,雷帕霉素组为细胞孵育液+10^(-6)moL/L AngⅡ+10^(-7)mol/L雷帕霉素。各组干预时间均为24 h。比较各组细胞的增殖活力,Ⅰ、Ⅲ型胶原蛋白含量及钙黏蛋白E(E-cad)、α平滑肌肌动蛋白(α-SMA)、微管相关蛋白1轻链3Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ)、Beclin1和p62蛋白表达。结果AngⅡ组细胞增殖活力、Ⅰ型、Ⅲ型胶原蛋白含量及α-SMA、p62蛋白表达水平均明显高于正常对照组(均P<0.05),E-cad、LC3-Ⅱ/Ⅰ及Beclin1蛋白表达均明显低于正常对照组(均P<0.05);双氢青蒿素组和雷帕霉素组细胞增殖活力、Ⅰ型和Ⅲ型胶原蛋白含量及α-SMA、p62蛋白水平均明显低于正常对照组(均P<0.05),E-cad、LC3-Ⅱ/Ⅰ及Beclin1蛋白表达水平均明显高于AngⅡ组(均P<0.05);双氢青蒿素组细胞增殖活力、Ⅰ型和Ⅲ型胶原蛋白含量及α-SMA、p62蛋白表达水平均高于雷帕霉素组(均P<0.05),E-cad、LC3-Ⅱ/Ⅰ及Beclin1蛋白表达水平均低于雷帕霉素组(均P<0.05)。结论双氢青蒿素能降低AngⅡ诱导的EECs增殖活力以及分泌Ⅰ、Ⅲ型胶原蛋白的含量,抑制细胞转分化,这与其提高细胞自噬水平密切相关。Objective To investigate the effect of dihydroartemisinin on the transdifferentiation and autophagy protein expression of endometrial epithelial cells(EECs)induced by angiotensinⅡ(AngⅡ),and to explore the mechanism of dihydroartemisinin antagonizing endometrial fibrosis.Methods Human primary EECs were obtained and divided into the following groups:normal control group,AngⅠgroup,dihydroartemisinin group and rapamycin group.Normal control group:cell incubation solution,AngⅠgroup:cell incubation solution+10^(-6)mol/L AngⅠ,dihydroartemisinin group:cell incubation solution+10^(-6)mol/L AngⅠ+100 ng/mL dihydroartemisinin,rapamycin group:cell incubation solution+10-6mol/L AngⅠ+10^(-7)mol/L rapamycin.The intervention time of each group was 24 hours.Measure the proliferation activity of cells in each group;ELⅠSA measures the secretion of typeⅠand typeⅢcollagen by cells;Ⅰmmunoblotting was used to evaluate the levels of transdifferentiation proteins E-cad andα-SMA,autophagy proteins LC3-Ⅰ/Ⅰ,Beclin1 and p62.Results The cell proliferation activity,secretion levels of typeⅠ,typeⅢcollagen,protein expression level ofα-SMA,p62 in the AngⅠgroup were obviously higher than those in the normal control group(all P<0.05),while E-cad,LC3-Ⅱ/Ⅰand Beclin1 were obviously lower than those of the normal control group(both P<0.05);The cell proliferation activity,secretion content of typeⅠ,typeⅢcollagen,protein expression levels ofα-SMA,p62 in dihydroartemisinin group were obviously lower than those in the AngⅡgroup(all P<0.05),while E-cad,LC3-Ⅱ/Ⅰand Beclin1 were obviously higher than those of the AngⅠgroup(both P<0.05);The cell proliferation activity,secretion content of typeⅠ,typeⅢcollagen,protein expression level ofα-SMA,p62 in dihydroartemisinin group were obviously higher than those in rapamycin group(all P<0.05),while E-cad,LC3-Ⅱ/Ⅰand Beclin1 were obviously lower than those of the rapamycin group(both P<0.05).Conclusion Dihydroartemisinin can reduce the proliferation activity of E

关 键 词：双氢青蒿素 血管紧张素Ⅱ 子宫内膜上皮细胞 细胞转分化 自噬 

分 类 号：R711.74[医药卫生—妇产科学] R285.5[医药卫生—临床医学]