欧前胡素调节AKT/GSK3β/β-catenin通路对子痫前期大鼠滋养层细胞损伤的影响  

Effect of imperatorin on trophoblast cell damage in preeclampsia rats by regulating the AKT/GSK3β/β-catenin pathway

作　　者：张丽杰 姚姝 ZHANG Lijie;YAO Shu(Department of Obstetrics and Gynecology,Xi’an Gaoxin Hospital,Xi’an,Shaanxi 710000,China)

机构地区：[1]西安高新医院产二科,陕西西安710000

出　　处：《中国优生与遗传杂志》2024年第12期2487-2493,共7页Chinese Journal of Birth Health & Heredity

摘　　要：目的探究欧前胡素(Imp)是否可通过调节AKT/GSK3β/β-catenin通路来改善子痫前期(PE)大鼠滋养层细胞损伤。方法将大鼠分为CK组、Model组、Imp低剂量(Imp-L)组、Imp高剂量(Imp-H)组、Imp-H+MK-2206(AKT/GSK3β/β-catenin通路抑制剂)组,皮下注射N-硝基-L-精氨酸甲酯(L-NAME)建立PE大鼠模型。H-E染色观察胎盘组织形态;TUNEL染色检测胎盘组织细胞凋亡;测定胎盘组织SOD和CAT活性、MDA含量;Western blot检测胎盘组织E-cadherin、N-cadherin、vimentin和AKT/GSK3β/β-catenin通路相关蛋白表达水平;分离各组大鼠绒毛膜滋养层细胞,CCK-8法检测细胞增殖;Transwell实验检测细胞迁移和侵袭。结果与Model组相比,Imp-L组和Imp-H组大鼠胎盘组织形态有明显改善,胎盘组织细胞凋亡率、MDA含量、E-cadherin蛋白表达水平降低,胎盘组织SOD和CAT活性、N-cadherin、vimentin、p-AKT/AKT、p-GSK3β/GSK3β和β-catenin蛋白表达水平、滋养层细胞OD450值(48 h、72 h)、滋养层细胞迁移和侵袭个数升高(P<0.05);MK-2206可部分逆转Imp对PE大鼠胎盘组织和滋养层细胞损伤的改善作用(P<0.05)。结论Imp可降低PE大鼠滋养层细胞损伤和氧化应激,改善滋养层细胞增殖、迁移和侵袭功能,可能与激活AKT/GSK3β/β-catenin通路有关。Objective To explore whether imperatorin(Imp)can ameliorate trophoblastic cell injury in preeclampsia(PE)rats by regulating the AKT/GSK3β/β-catenin pathway.Methods Rats were separated into CK group,Model group,low-dose(Imp-L)group,high-dose(Imp-H)group,and Imp-H+MK-2206(AKT/GSK3β/β-catenin pathway inhibitor)group.The PE rat model was established by subcutaneous injection of N-nitro-l-arginine methyl ester(L-NAME).H-E staining was applied to observe the morphology of placental tissue.Detect apoptosis in placental tissue cells by TUNEL staining.The activity of SOD and CAT and the content of MDA in placenta tissue were detected.Detect the expression levels of E-cadherin,N-cadherin,vimentin,and AKT/GSK3β/β-catenin pathway related proteins in placental tissue by Western blot.The trophoblast cells of rats in each group were isolated,CCK-8 method was applied to detect cell proliferation.Transwell experiment was applied to detect cell migration and invasion.Results Compared with the Model group,there was a significant improvement in the morphology of rat placental tissue in the Imp-L and Imp-H groups,the apoptosis rate of placental tissue cells,MDA content,and E-cadherin protein expression level decreased,the activities of SOD and CAT in placental tissue,N-cadherin,vimentin,p-AKT/AKT,p-GSK3β/GSK3βandβ-catenin protein expression levels,OD450 values of trophoblast cells(48 h,72 h),and the numbers of trophoblast cell migration and invasion increased(P<0.05).MK-2206 was able to partially reverse the improvement effect of Imp on placental tissue and trophoblast cell damage in PE rats(P<0.05).Conclusion Imp can reduce trophoblast cell damage and oxidative stress in PE rats,improve the proliferation,migration,and invasion functions of trophoblast cells,and may be related to the activation of the AKT/GSK3β/β-catenin pathway.

关 键 词：欧前胡素 AKT/GSK3β/β-catenin通路 子痫前期 滋养层细胞 

分 类 号：R714.244[医药卫生—妇产科学]