摘要
目的:探讨晚期糖基化终末产物受体(RAGE)/核转录因子-κB(NF-κB)通路对妊娠期糖尿病(GDM)大鼠胎盘滋养细胞凋亡及胎盘屏障功能改变的影响。方法:将受孕雌性SD大鼠随机分为正常妊娠组、模型组(GDM组)、RAGE抑制剂组(FPS-ZM1组)、RAGE抑制剂阴性对照组(FPS-ZM1 NC组)、RAGE激活剂组(RAGE组)、RAGE激活剂阴性对照组(RAGE NC组),每组20只。除正常妊娠组外,其余各组均建立GDM模型,并在妊娠第5天开始给药,连续给药2周后,比较各组空腹血糖(FBG)、晚期糖基化终末产物(AGE)、胎盘重量、胎鼠重量、胎盘通透性、胎盘滋养细胞凋亡率;胎盘组织RAGE、NF-κB、紧密连接蛋白(TJ)、囊膜蛋白-2(Syncytin-2)、调解超家族蛋白2 A(MFSD2 A)、抗凋亡蛋白B淋巴细胞瘤-2(Bcl-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达水平的差异。结果:与正常妊娠组相比,GDM组大鼠FBG及AGE水平、胎盘重量及胎鼠重量、胎盘组织伊文思蓝(EB)含量、RAGE和NF-κB阳性表达水平、IL-6、TNF-α、Bcl-2蛋白表达均升高((印)P(正)<0.05),胎盘滋养细胞凋亡率、TJ、Syncytin-2、MFSD2 A蛋白表达均降低((印)P(正)<0.05)。与GDM组相比,RAGE组大鼠FBG及AGE水平、胎盘重量及胎鼠重量、胎盘组织EB含量、RAGE和NF-κB阳性表达水平、IL-6、TNF-α、Bcl-2蛋白表达均升高((印)P(正)<0.05),胎盘滋养细胞凋亡率、TJ、Syncytin-2、MFSD2 A蛋白表达均降低((印)P(正)<0.05);FPS-ZM1组大鼠FBG及AGE水平、胎盘及胎鼠重量、胎盘组织EB含量、RAGE和NF-κB阳性表达水平、IL-6、TNF-α、Bcl-2蛋白表达均降低((印)P(正)<0.05),胎盘滋养细胞凋亡率、TJ、Syncytin-2、MFSD2 A蛋白表达均升高((印)P(正)<0.05)。GDM组、RAGE NC组及FPS-ZM1 NC组大鼠上述指标差异均无统计学意义((印)P(正)>0.05)。结论:RAGE/NF-κB通路激活参与GDM大鼠胎盘滋养细胞凋亡及胎盘屏障功能损伤过程,抑制RAGE/NF-κB通路激活可促进胎盘滋养细胞凋亡,改善胎盘屏障功能,缓解GDM大鼠胎盘及胎鼠过度增长发育。
Objective:To investigate the effects of the receptor of advanced glycation end products(RAGE)/nuclear transcription factor-κB(NF-κB)pathway on placental trophoblast cells apoptosis and placental barrier function in rats with gestational diabetes mellitus(GDM).Methods:Pregnant female SD rats were randomly divided into normal pregnancy group,model group(GDM group),RAGE inhibitor group(FPS-ZM1 group),RAGE inhibitor negative control group(FPS-ZM1 NC group),RAGE activator group(RAGE group),and RAGE activator negative control group(RAGE NC group),with 20 rats in each group.The GDM model was established in all groups except the normal pregnancy group,and the drug was administered on the 5th day of pregnancy.After 2 weeks of continuous administration,the differences in the expression levels of fasting blood glucose(FBG),advanced glycation end products(AGEs),placenta weight,fetal mouse weight,placental permeability,and apoptosis rate of placental trophoblast cells,placental tissue RAGE,NF-κB,tight junction(TJ),Syncytin-2,major facilitator superfamily domain-containing protein 2A(MFSD2 A),anti-apoptotic protein B-cell lymphoma-2(Bcl-2),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were compared among the groups.Results:Compared with the normal pregnancy group,the levels of FBG and AGE,the weight of placenta and fetal rats,the Evans blue(EB)content of placental tissue,the positive expression levels of RAGE and NF-κB in placental tissue,the protein expression of IL-6,TNF-α,and Bcl-2 in GDM group were all significantly increased(P<0.05),the apoptosis rate of placental trophoblast cells and the protein expression of TJ,Syncytin-2,and MFSD2 A protein in placental tissue were decreased(P<0.05).Compared with GDM group,the levels of FBG and AGE,the weight of placenta and fetal rats,the EB content of placental tissue,the positive expression levels of RAGE and NF-κB in placental tissue,the protein expression of IL-6,TNF-α,and Bcl-2 were much higher in RAGE group(P<0.05).Correspondingly,the apoptosis rate of placental trophoblast cells and the protein expression of TJ,Syncytin-2,and MFSD2 A protein in placental tissue were much lower(P<0.05);In FPS-ZM1 group,the levels of FBG and AGEs,the weight of placenta and fetal rats,the EB content of placental tissue,the positive expression levels of RAGE and NF-κB in placental tissue,the protein expression of IL-6,TNF-α,and Bcl-2 were decreased(P<0.05),while the apoptosis rate of placental trophoblast cells and the protein expression of TJ,Syncytin-2 and MFSD2 A protein in placental tissue were elevated(P<0.05).There was no statistically significant difference in the above indexes among GDM group,RAGE NC group,and FPS-ZM1 NC group(P>0.05).Conclusions:The activation of RAGE/NF-κB pathway is involved in the process of placental trophoblast apoptosis and impairment of placental barrier function in rats with GDM.Inhibition of RAGE/NF-κB pathway activation can promote placental trophoblast apoptosis,improve placental barrier function,and alleviate placenta and fetal overgrowth development in rats with GDM.
作者
彭青
温彦静
李茜
李曼
常美英
PENG Qing;WEN Yanjing;LI Qian(Department of Obstetrics,Hebei Hospital of Traditional Chinese Medicine,Shijiazhuang Hebei 050032,China)
出处
《实用妇产科杂志》
CAS
CSCD
北大核心
2023年第2期126-131,共6页
Journal of Practical Obstetrics and Gynecology
基金
河北省医学科学研究课题计划项目(编号:20200849)。
关键词
妊娠期糖尿病
晚期糖基化终末产物受体/核转录因子-κB通路
胎盘滋养细胞
凋亡
胎盘屏障功能
Gestational diabetes mellitus
Receptor of advanced glycation end products/Nuclear transcription factor-κB pathway
Placental trophoblast cells
Apoptosis
Placental barrier function
