丹参酮ⅡA通过HIF-1α/VEGF信号通路对胚泡植入障碍小鼠子宫内膜容受性的影响  

Impact of tanshinoneⅡA on endometrial receptivity in mice with blastocyst implantation dysfunction through the HIF⁃1α/VEGF signaling pathway

作　　者：冯翠娥 周云 FENG Cui-'e;ZHOU Yun(Reproductive Medicine Center of the Second People's Hospital of Anhui Province,Hefei,An-hui 230041,China)

机构地区：[1]安徽省第二人民医院生殖医学中心,安徽合肥230041

出　　处：《解剖学研究》2023年第3期193-198,共6页Anatomy Research

基　　金：安徽省教育厅高校科学研究项目(KJ2020A0859)。

摘　　要：目的 探讨丹参酮ⅡA通过HIF-1α/VEGF信号通路对胚泡植入障碍小鼠子宫内膜容受性的影响。方法 将C57BL/6小鼠随机平分为对照组(CON组)、Model组、丹参酮ⅡA组(10 mg/kg)、PX-478组(40 mg/kg HIF-1 α/VEGF通路抑制剂PX-478)、丹参酮ⅡA+PX-478组(10 mg/kg丹参酮ⅡA+40 mg/kg PX-478),每组15只。除CON组外,其余组小鼠皮下注射吲哚美辛建立胚泡植入障碍模型。ELISA试剂盒检测激素水平;台盼蓝染色观察胚泡植入位点数量;HE染色检查子宫病理变化;免疫组化染色检测子宫VEGF和Ang-1阳性细胞数;Western blot检测HOXA10、LIF蛋白以及HIF-1α/VEGF通路蛋白表达。结果 CON组小鼠子宫内膜结构完整,上皮细胞整齐排列,血管和腺体清晰可见;Model组子宫内膜腺体和血管稀少,子宫内膜明显变薄。Model组较CON组小鼠血清中P、FSH含量、胚泡植入位点数量、VEGF和Ang-1阳性细胞数、HOXA10、LIF、HIF-1α、VEGF、VEGFR2蛋白水平显著降低(P<0.05),E2、LH含量显著升高(P<0.05);与Model组相比,丹参酮ⅡA组小鼠血清中P、FSH含量、胚泡植入位点数量、VEGF和Ang-1阳性细胞数、HOXA10、LIF、HIF-1α、VEGF、VEGFR2蛋白水平显著升高(P<0.05),E2、LH含量显著降低(P<0.05);而PX-478组结果与丹参酮ⅡA组趋势相反;PX-478消除了丹参酮ⅡA对胚泡植入障碍小鼠子宫内膜容受性的有利影响。结论 丹参酮ⅡA可能通过上调HIF-1α/VEGF信号通路对胚泡植入障碍小鼠子宫内膜容受性起到改善作用。Objective To investigate the impact of tanshinoneⅡA on endometrial receptivity in mice with blastocyst implantation dysfunction through the HIF⁃1α/VEGF signaling pathway.Methods C57BL/6 mice were randomly grouped into control group(CON group),model group,tanshinoneⅡA group(10 mg/kg),PX⁃478 group(40 mg/kg HIF⁃1α/VEGF pathway inhibitor PX⁃478),and tanshinoneⅡA+PX⁃478 group(10 mg/kg tanshi⁃noneⅡA+40 mg/kg PX⁃478),with 15 mice in each group.In addition to the CON group,other groups of mice were subcutaneously injected with indomethacin to establish blastocyst implantation dysfunction models.ELISA kit was ap⁃plied to detect hormone levels;Trypan blue staining was applied to observe the number of blastocyst implantation sites;HE staining was applied to examine the pathological changes of the uterus;immunohistochemical staining was applied to detect the numbers of VEGF and Ang⁃1 positive cells in the uterus;Western blot was applied to detect the expression of HOXA10,LIF proteins,and HIF⁃1α/VEGF pathway protein.Results In CON group,the endometri⁃al structure was intact,epithelial cells were orderly arranged,and blood vessels and glands were clearly visible;in the Model group,endometrial glands and blood vessels were sparse,and the endometrium became significantly thinner.The serum contents of P and FSH,the number of blastocyst implantation sites,the numbers of VEGF and Ang⁃1 positive cells,the protein levels of HOXA10,LIF,HIF⁃1α,VEGF,and VEGFR2 in the model group were signif⁃icantly lower than those in the CON group(P<0.05),the contents of E2 and LH were significantly lower(P<0.05);compared with the model group,the serum contents of P and FSH,the number of blastocyst implantation sites,the numbers of VEGF and Ang⁃1 positive cells,the protein levels of HOXA10,LIF,HIF⁃1α,VEGF,and VEGFR2 in the tanshinoneⅡA group were significantly higher(P<0.05),the contents of E2 and LH were significantly lower(P<0.05);the trends of PX⁃478 group were opposite to that of tanshinone IIA group

关 键 词：丹参酮ⅡA HIF-1α/VEGF信号通路 胚泡植入障碍 子宫内膜容受性 

分 类 号：R285.5[医药卫生—中药学]