白芍总苷对子宫内膜异位症大鼠异位组织HIF-1α/VEGF信号通路的影响  

Effect of total glucosides of paeony on HIF-1α/VEGF signal pathway in ectopic tissue of rats with endometriosis

作　　者：包利利 赵达 俞岩 王晓黎 BAO Lili;ZHAO Da;YU Yan;WANG Xiaoli(Department of Gynecology,Hainan Women and Children’s Medical Center,Haikou,Hainan 571103,China)

机构地区：[1]海南省妇女儿童医学中心妇科,海南海口571103

出　　处：《中国优生与遗传杂志》2023年第4期689-695,共7页Chinese Journal of Birth Health & Heredity

摘　　要：目的 探究白芍总苷对子宫内膜异位症(EMs)大鼠缺氧诱导因子1α(HIF-1α)/血管内皮生长因子(VEGF)通路的影响。方法 取SD大鼠随机分为假手术组、模型组、白芍总苷组、HIF-1α激动剂(DMOG)组、HIF-1α/VEGF信号通路阻断剂(YC-1)组、白芍总苷+DMOG组,用自体子宫内膜移植法建立EMs模型。各组大鼠持续给药4周后,比较病灶体积,取异位内膜组织,H-E法检测各组子宫内膜组织形态;免疫组化法检测HIF-1α、VEGF、CD34表达;蛋白免疫印迹法(western blot)检测促血管生成素2(Ang-2)、基质金属蛋白酶9(MMP-9)、核转录因子κB(NF-κB)、磷酸化NF-κB(p-NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、前列腺素E2(PGE2)、雌激素受体β(ERβ)、基质环氧酶2(COX-2)、凋亡信号调节激酶1(ASK1)表达水平。结果 与假手术组相比,模型组大鼠异位内膜病灶体积增大,异位内膜组织腺体及间质细胞增多,血管增生严重,HIF-1α介导的血管生成、雌激素分泌相关通路、炎症反应等蛋白表达升高(P<0.05)。与模型组相比,白芍总苷组及YC-1组大鼠异位内膜病灶体积减小,HIF-1α/VEGF通路表达降低,HIF-1α介导的血管生成、雌激素分泌、炎症反应等相关蛋白表达降低(P<0.05);DMOG组大鼠异位内膜病灶体积、HIF-1α/VEGF通路表达升高。DMOG能逆转白芍总苷抑制血管生成、雌激素分泌及炎症反应的作用(P<0.05)。结论 白芍总苷可能通过抑制HIF-1α介导的血管生成、雌激素水平升高、炎症反应激活,来延缓EMs异位病灶的增长。Objective To explore the effect of total glucosides of paeony on hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway in rats with endometriosis(EMs).Methods SD rats were randomly divided into sham operation group,model group,total glucosides of paeony group,HIF-1αagonist(DMOG)group,HIF-1α/VEGF signal pathway blocker(YC-1)group,total glucosides of paeony+DMOG group,an EMs model was established with autologous endometrial transplantation.After 4 weeks of continuous administration,the lesion volume was compared,the ectopic endometrial tissue was taken,and the endometrial tissue morphology was detected by H-E method.The expression of HIF-1α,VEGF and CD34 were detected by immunohistochemistry.The expression levels of angiopoietin 2(Ang-2),matrix metalloproteinase 9(MMP-9),nuclear transcription factor-κB(NF-κB),phosphorylated NF-κB(p-NF-κB),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),prostaglandin E2(PGE2),estrogen receptorβ(ERβ),matrix cyclooxygenase 2(COX-2),and apoptosis signal-regulated kinase 1(ASK1)were detected by western blot.Results Compared with the sham operation group,the volume of ectopic endometrial lesions in the model group increased,the number of glands and interstitial cells of the ectopic endometrial tissue increased,the vascular proliferation was severe,and the expression of HIF-1α-mediated angiogenesis,estrogen secretion-related pathway,inflammation and other proteins increased(P<0.05).Compared with the model group,the volume of ectopic endometrial lesions in the total glucosides of paeony group and YC-1 group decreased,and the expression of HIF-1α/VEGF pathway decreased,the expression of HIF-1α-mediated angiogenesis,estrogen secretion,inflammation and other proteins decreased(P<0.05).The volume of ectopic endometrial lesions and the expression of HIF-1α/VEGF pathway in the DMOG group increased further.DMOG could reverse the inhibitory effect of total glucosides on angiogenesis,estrogen secretion and inflammation(P<0.05

关 键 词：白芍总苷 子宫内膜异位症 缺氧诱导因子1α/血管内皮生长因子通路 

分 类 号：R285.5[医药卫生—中药学]