肥胖合并妊娠期糖尿病产妇胎盘滋养层细胞凋亡机制  

Mechanism of apoptosis of placental trophoblasts in puerperae with obesity and gestational diabetes mellitus

作　　者：周斌 段洋[1] ZHOU Bin;DUAN Yang(Department of Neonatology,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院新生儿科,天津300211

出　　处：《军事医学》2024年第4期281-287,共7页Military Medical Sciences

基　　金：天津市教委科研计划项目(自然科学)(2020KJ173)。

摘　　要：目的探究在肥胖合并妊娠期糖尿病产妇中,高血糖、高血脂促进胎盘滋养层细胞凋亡的机制。方法留取天津医科大学第二医院产科2020年1月至2023年1月收治的健康(NC)产妇、妊娠期糖尿病(GDM)产妇、肥胖(OB)产妇和肥胖合并妊娠期糖尿病(OB+GDM)产妇各20例的胎盘,分别予HE染色、免疫组化检测胎盘病理变化及凋亡相关蛋白的表达,通过Western印迹检测哺乳动物不育系20样激酶1(MST1)、c-Jun氨基末端激酶(JNK)、Bcl-2相关X蛋白(BAX)、B细胞淋巴瘤-2基因(BCL-2)、半胱氨酸蛋白水解酶3(CASP3)等凋亡相关蛋白的表达。结果胎盘HE染色发现,高血糖、高血脂可导致胎盘合体滋养细胞和细胞滋养细胞相对减少且大小不一;TUNEL法发现,高血糖和高血脂导致滋养层细胞凋亡增加,以合体滋养细胞凋亡为主,OB+GDM组凋亡最为严重;免疫组化检测发现,高血糖、高血脂可以诱导胎盘凋亡相关蛋白MST1、JNK的表达增加;Western印迹检测发现,MST1-JNKBAX-CASP3凋亡调控通路可能参与胎盘滋养层细胞凋亡过程。结论肥胖合并妊娠期糖尿病产妇的胎盘滋养层细胞可能在高血糖、高脂血症形成的内环境下,过度产生活性氧,通过MST1-JNK-BAX-CASP3凋亡调控通路介导胎盘滋养层细胞的凋亡,从而影响胎盘功能。Objective To explore the mechanism by which hyperglycemia and hyperlipidemia promote apoptosis of placental trophoblasts in obese puerperae with gestational diabetes mellitus.Methods The placentas of 20 healthy(NC)puerperae,20 gestational diabetes mellitus(GDM)puerperae,20 obese(OB)puerperae and 20 obese puerperae combined with gestational diabetes mellitus(OB+GDM)were collected at the Second Hospital of Tianjin Medical University between January 2020 and January 2023.Placental pathology was detected via HE staining and the expressions of apoptosisrelated proteins by immunohistochemistry.The expressions of mammalian sterile 20-like kinase 1(MST1),c-Jun N-terminal kinase(JNK),Bcl-2 associated X protein(BAX),B-cell lymphoma-2(Bcl-2),cysteinyl aspartate specific proteinase(caspase 3)and other apoptosis-related proteins were detected by Western blotting.Results HE staining revealed that hyperglycemia and hyperlipidemia could lead to a relative decrease and varying sizes of syncytial trophoblasts and cytotrophoblasts in placentas.The TUNEL method found that hyperglycemia and hyperlipidemia led to increased apoptosis in trophoblasts,particularly in syncytial trophoblasts,with the most pronounced apoptosis in the obese combined with GDM group.Immunohistochemical detection of placentas revealed that hyperglycemia and hyperlipidemia could increase the expressions of apoptosis-related proteins MST1 and JNK.The regulatory pathway of MST1-JNK-BAX-CASP3 apoptosis was found to be involved in the apoptotic process of placental trophoblasts by Western blotting.Conclusion The placental trophoblasts of obese women with gestational diabetes mellitus may overproduce reactive oxygen species in the internal environment formed by hyperglycemia and hyperlipidemia,which mediates the apoptosis of placental trophoblasts through the regulatory pathway of MST1-JNK-BAX-CASP3 apoptosis,thus affecting the placental function.

关 键 词：胎盘 滋养层 妊娠期肥胖 糖尿病 妊娠 细胞凋亡 

分 类 号：R587.1[医药卫生—内分泌]