前列腺素F2α在小鼠月经发生过程中的作用机制  

Mechanism of Prostaglandin F2α Action during Menstruation in Mice

作　　者：田聪贵 徐妹 潘海波 王小敏 TIAN Cong-gui;XU Mei;PAN Hai-bo;WANG Xiao-min(Department of Obstetrics,the Second People's Hospital of Longgang District,Shenzhen 518000,China;Department of Gynecology,the Second People's Hospital of Longgang District,Shenzhen 518000,China;Department of Anesthesiology,the Second People's Hospital of Longgang District,Shenzhen 518000,China)

机构地区：[1]深圳市龙岗区第二人民医院产科,广东深圳518000 [2]深圳市龙岗区第二人民医院妇科,广东深圳518000 [3]深圳市龙岗区第二人民医院麻醉科,广东深圳518000

出　　处：《南昌大学学报（医学版）》2023年第6期15-20,26,共7页Journal of Nanchang University：Medical Sciences

基　　金：广东省卫健委科研项目(2021AW203)。

摘　　要：目的 探究子宫内膜中的前列腺素F2α(PGF2α)在月经发生过程中对子宫内膜修复的作用。方法 建立小鼠月经样模型,在黄体酮(P4)植入物移除时(T0)或移除后8 h(T8)或24 h(T24)通过颈椎脱位处死小鼠,并收集子宫。使用免疫组织化学研究哌莫硝唑和PGF2α蛋白染色的定位。在P4植入物移除前1 d给予小鼠AL-8810处理,以抑制PGF2与其受体的结合。通过组织学分析对小鼠子宫内膜的破裂/修复阶段进行分级,用qPCR检测PGF2α的下游靶标(VEGF、Glut1)和炎症介质(CXCL1、TNF-α)表达。通过体外细胞培养实验观察来自PGF2α沉默的人内皮细胞条件培养基对人脐带血管内皮细胞(HUVEC)分支形成的影响。结果 T8时,月经样模型小鼠子宫内膜组织中哌莫硝唑染色和PGF2α染色百分比较T0时显著增加(P<0.05),并且T24时哌莫硝唑染色和PGF2α染色百分比较T8时显著减少(P<0.05)。T24时,溶剂对照组子宫内膜修复明显,而AL-8810组与T8时相比差异无统计学意义(P>0.05)。与溶剂对照组相比,AL-8810组小鼠的子宫内膜中VEGF mRNA和Glut1 mRNA在T8时显著降低(P<0.001),并且CXCL1 mRNA和TNF-α mRNA在T24时显著降低(P<0.01)。向HUVEC细胞中添加在缺氧条件下生长的转染sh-PGF2α的上皮细胞条件培养基,其分支数目显著减少(P<0.01)。结论 缺氧和PGF2α在生理性子宫内膜修复中发挥重要作用,促进PGF2α生成可作为月经失调的潜在治疗靶点。Objective To investigate the role of prostaglandin F2α(PGF2α) in endometrial repair during menstruation.Methods A mouse menstrual-like model was established.The mice were killed by cervical dislocation to collect the uterus at the time of progesterone(P4) implant removal(T0),and 8 h(T8) and 24(T24) h after P4 withdrawal.The localization of pemonidazole and PGF2α was observed by immunohistochemical staining.Furthermore,the mice were given AL-8810 at 1 day before P4 withdrawal to inhibit the binding of PGF2α to its receptor.Histological analysis was used to classify the rupture/repair stage,and qPCR was performed to detect the expression of PGF2α downstream targets(VEGF and Glut1) and inflammatory mediators(CXCL1 and TNF-α).In addition,in vitro experiments were conducted to observe the effect of conditioned medium from PGF2α-silenced human endothelial cells on branch formation of human umbilical vascular endothelial cells(HUVEC).Results The percentages of pimonidazole staining and PGF2α staining at T8 were higher than those at T0,and those at T24 were lower than those at T8(P<0.05).At T24,endometrial repair was significant in the vehicle group,while was not different from that at T8 in the AL-8810 group.Compared with the vehicle group,AL-8810 treatment reduced uterine expression of VEGF and Glut1 at T8(P<0.001),as well as the expression of CXCL1 and TNF-α at T24(P<0.01).The number of branches was significantly decreased after HUVECs were supplemented with conditioned medium from sh-PGF2α-transfected epithelial cells under hypoxia(P<0.01).Conclusion Hypoxia and PGF2α play important roles in physiological endometrial repair,and promoting PGF2α production may have potential therapeutic value in the treatment of menstrual disorders.

关 键 词：前列腺素F2Α 月经 子宫内膜 缺氧 动物 实验 小鼠 

分 类 号：R339.22[医药卫生—人体生理学]