淫羊藿苷通过HIF-1α/VEGF通路介导的血管生成调节大鼠种植窗期子宫内膜容受性  

Icariin regulates endometrial receptivity at implantation window in rats through HIF-1α/VEGF pathway mediated angiogenesis

作　　者：于倩 刘静 李翠[1] 许晓东 易建平[1] YU Qian;LIU Jing;LI Cui;XU Xiaodong;YI Jianping(Tangshan City Maternal and Child Health Care Hospital,Tangshan,Hebei 063000,China)

机构地区：[1]唐山市妇幼保健院,河北唐山063000

出　　处：《中国优生与遗传杂志》2023年第7期1321-1328,共8页Chinese Journal of Birth Health & Heredity

摘　　要：目的探究淫羊藿苷通过缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)通路介导的血管生成调节大鼠种植窗期子宫内膜容受性的机制。方法取SD雌性大鼠通过灌胃羟基脲+肾上腺素皮下注射的方法建立子宫内膜容受障碍模型,随机分为模型组、淫羊藿苷低剂量(10 mg/kg)组、淫羊藿苷高剂量(20 mg/kg)组、淫羊藿苷高剂量(20 mg/kg)+空载组、淫羊藿苷高剂量(20 mg/kg)+HIF-1α敲低组,每组20只,另选20只SD雌性大鼠灌胃+皮下注射等剂量生理盐水做对照组,将各组雌鼠与雄鼠合笼得到孕鼠并分组处理后,测定各组大鼠性激素[雌激素(E2)、孕酮激素(P)]水平、平均着床胚胎数;免疫组织化学染色检测各组大鼠子宫内膜微血管密度(MVD);扫描电子显微镜检测各组大鼠子宫内膜超微结构;免疫组织化学染色和免疫印迹检测各组大鼠子宫内膜组织HIF-1α/VEGF通路蛋白表达。结果与对照组相比,模型组大鼠子宫内膜表面附着大量短细微绒毛,未发现胞饮突,血清E2与P水平、平均着床胚胎数、子宫内膜MVD、HIF-1α与VEGF蛋白表达明显降低(P<0.05);与模型组相比,淫羊藿苷低、高剂量组大鼠子宫内膜表面附着的短细微绒毛减少,胞饮突增多,血清E2与P水平、平均着床胚胎数、子宫内膜MVD、HIF-1α与VEGF蛋白表达均升高(P<0.05);与淫羊藿苷高剂量组相比,淫羊藿苷高剂量+HIF-1α敲低组大鼠子宫内膜表面附着的短细微绒毛增多,胞饮突减少,血清E2与P水平、平均着床胚胎数、子宫内膜MVD、HIF-1α与VEGF蛋白表达降低(P<0.05)。结论淫羊藿苷可通过上调HIF-1α/VEGF通路而提高雌激素及孕激素分泌水平,从而增强种植窗期大鼠血管生成,改善其子宫内膜容受性,最终促使胚胎成功着床。Objective To explore the mechanism of icariin regulating endometrial receptivity at implantation window in rats through hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway mediated angiogenesis.Methods Female SD rats were randomly divided into model group,icariin low-dose(10 mg/kg)group,icariin high-dose(20 mg/kg)group,icariin high-dose(20 mg/kg)+no-load group,and icariin high-dose(20 mg/kg)+HIF-1αknockdown group,20 rats in each group,another 20 female SD rats were selected as the control group by gavage+subcutaneous injection of equal dose of normal saline,pregnant rats were obtained by combining female rats and male rats in each group,and then divided into groups for treatment,the levels of sex hormones[estrogen(E2),progesterone(P)]and the average number of embryos implanted in each group were measured.The microvessel density(MVD)of endometrium in each group was detected by immunohistochemical staining.The ultrastructure of endometrium in each group was detected by scanning electron microscope.The expression of HIF-1α/VEGF pathway protein in rat endometrium was detected by immunohistochemistry and western blot.Results Compared with the control group,a large number of short and fine villi were attached to the endometrial surface of the model group rats,and no pinocytosis was found,the levels of serum E2 and P,average number of implanted embryos,positive expressions of MVD,and the protein expressions of HIF-1αand VEGF decreased obviously(P<0.05).Compared with the model group,the number of short and fine villi attached to the endometrial surface of rats in the icariin low and high-dose group decreased,and the number of pinocytosis increased,the levels of serum E2 and P,average number of implanted embryos,positive expressions of MVD,and the protein expressions of HIF-1αand VEGF increased(P<0.05).Compared with icariin high-dose group,the short and fine villi attached to the endometrial surface of the rats in the icariin high-dose+HIF-1αknockdown group increased,and the pinocyto

关 键 词：淫羊藿苷 HIF-1α/VEGF 血管生成 子宫内膜容受性 

分 类 号：R285.5[医药卫生—中药学]