南蛇藤素调节Hippo-YAP信号通路对子宫内膜异位症大鼠血管生成的影响  

Impact of celastrol on angiogenesis in rats with endometriosis by regulating Hippo-YAP signal pathway

作　　者：张静 高冬冬 谷灿灿 陈静 ZHANG Jing;GAO Dongdong;GU Cancan;CHEN Jing(Medical College,Huanghuai University,Zhu-madian 463000,China;Department of Oncology,Zhumadian Central Hospital,Zhumadian 463003,China;Department of Gynecology,Shanghai Traditional Chinese Medicine Hospital,Shanghai 200071,China)

机构地区：[1]黄淮学院医学院,驻马店463000 [2]驻马店市中心医院肿瘤科,驻马店463003 [3]上海市中医医院妇科,上海200071

出　　处：《中国免疫学杂志》2024年第11期2330-2334,2342,共6页Chinese Journal of Immunology

基　　金：上海市2020年度“科技创新行动计划”医学创新研究专项项目(20Y21901400)。

摘　　要：目的:探究南蛇藤素(CEL)对子宫内膜异位症(EM)大鼠血管生成的影响及其对Hippo-YAP信号通路的调节机制。方法:将SD雌性大鼠分为6组:假手术组、模型组、阳性药物组(孕三烯酮)、Verteporfin组(YAP抑制剂)、CEL低、高剂量组,每组12只。检测大鼠子宫内膜的重量和体积;HE染色观察大鼠子宫内膜组织形态变化;免疫组化检测大鼠子宫内膜组织中微血管密度(MVD);ELISA法检测大鼠血清中血管内皮生长因子(VEGF)、TNF-α、IL-1β、IL-6的表达;Western blot检测大鼠子宫内膜组织中VEGF、YAP蛋白表达水平。结果:与假手术组相比,模型组EM大鼠可见明显的异位子宫内膜组织病灶,间质细胞数量增加,血管增生明显,子宫内膜组织的重量、体积、MVD及VEGF、TNF-α、IL-1β、IL-6的含量、YAP、TAZ、VEGF受体2(VEGFR2)蛋白表达水平均升高(P<0.05);与模型组相比,阳性药物组、Verteporfin组和CEL低、高剂量组EM大鼠异位子宫内膜组织逐渐脱落,间质细胞数量减少,结构疏松,且血管明显减少,子宫内膜组织的重量、体积、MVD及VEGF、TNF-α、IL-1β、IL-6的含量、YAP、TAZ、VEGFR2蛋白表达水平均降低(P<0.05)。结论:CEL可以通过抑制Hippo-YAP信号通路来抑制EM大鼠的血管生成。Objective:To explore the impact of celastrol(CEL)on angiogenesis in rats with endometriosis(EM)and its regu-latory mechanism on Hippo-YAP signal pathway.Methods:SD female rats were grouped into six groups:sham operation group,model group,positive drug group(gestrinone),Verteporfin group(YAP inhibitor),low and high doses CEL groups,with 12 rats in each group.The weight and volume of rat endometrium were measured;HE staining was applied to observe the histological changes of rat endometrium;the microvessel density(MVD)in rat endometrium was detected by immunohistochemistry;the expressions of vascular endothelial growth factor(VEGF),TNF-α,IL-1βand IL-6 in rat serum were detected by ELISA;Western blot was applied to detect the expressions of VEGF and YAP proteins in rat endometrium.Results:Compared with sham operation group,the EM rats in model group showed obvious ectopic endometrial tissue lesions,increased number of interstitial cells,and obvious vascular proliferation,the weight,volume,MVD,the contents of VEGF,TNF-α,IL-1β,IL-6,and the expression levels of YAP,TAZ,and VEGF receptor 2(VEGFR2)proteins in endometrial tissue increased(P<0.05);compared with model group,the ectopic endometrium tissue of EM rats in positive drug group,Verteporfin group and low and high dose CEL groups gradually fell off,the number of interstitial cells were decreased,the structure was loose,and the blood vessels were significantly reduced,the weight,volume,MVD,the contents of VEGF,TNF-α,IL-1β,IL-6,and the expression levels of YAP,TAZ,and VEGFR2 proteins in endometrial tissue were decreased(P<0.05).Conclusion:CEL can inhibit angiogenesis in EM rats by inhibiting Hippo-YAP signal pathway.

关 键 词：南蛇藤素 Hippo-YAP信号通路 子宫内膜异位症 血管生成 

分 类 号：R711.71[医药卫生—妇产科学]