补肾温阳化瘀方调节Notch1/Twist1介导的上皮-间质转化治疗子宫内膜异位症的机制研究
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1.河北中医药大学;2.河北省中西医结合生殖疾病协同创新中心

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国家自然科学基金资助项目;河北省自然科学基金资助项目


Study on the mechanism of the Formula for Bushen Wenyang Huayu Decoctionin regulating Notch1/ Twist1-mediated Epithelial-mesenchymal transition in the treatment of endometriosis
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1.Hebei university of Chinese Medicine;2.Hebei Collaborative Innovation Center of Integrated Traditional and Western Medicine on Reproductive Disease

Fund Project:

The National Natural Science Foundation of China ; The Natural Science Foundation of Hebei Province

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    摘要:

    目的:探讨补肾温阳化瘀方调节Notch1/Twist1信号通路介导的上皮-间质转化(Epithelial-mesenchymal transition,EMT)治疗子宫内膜异位症(Endometriosis,EMs)的作用机制。方法:造模完成后观察异位灶重量、体积和粘连程度;ELISA测定血清中性激素的水平;免疫组织化学法及Western blot检测E-cadherin、N-cadherin、Vimentin、及Notch1、Twist1蛋白的表达;Real-Time PCR检测E-cadherin、N-cadherin、Vimentin、及Notch1、Twist1的表达。结果:与假手术组比较,模型组血清中E2、P、FSH、LH含量显著升高(P<0.05),子宫组织中N-cadherin、Vimentin、Notch1、Twist1蛋白及mRNA水平显著升高(P<0.01,P<0.05),E-cadherin蛋白及mRNA水平显著降低(P<0.01)。与模型组比较,中药高、低剂量组及西药组异位灶体积明显减小(P<0.05,P<0.01),E2、P、FSH、LH水平显著升高(P<0.05),子宫及异位灶组织中N-cadherin、Vimentin及Notch1、Twist1蛋白及mRNA水平显著下降(P<0.01,P<0.05),E-cadherin蛋白及mRNA水平显著升高(P<0.01)。结论:补肾温阳化瘀方能显著抑制EMs疾病进展,其作用机制可能与下调Notch1/Twist1信号通路的表达,从而调控EMs疾病上皮-间质转化进程有关。

    Abstract:

    (1.Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, Hebei university of Chinese Medicine ,Shijiazhuang, Hebei 050091;2.Hebei Collaborative Innovation Center of Integrated Traditional and Western Medicine on Reproductive Disease,Shijiazhuang, Hebei 050091):Objective:To explore the mechanism of the Bushen Wenyang Huayu Formula in regulating the Notch1/Twist1 signaling pathway-mediated epithelial-mesenchymal transition (EMT) in the treatment of endometriosis (EMs).Methods:After modeling, the weight,volume and adhesion degree of ectopic lesions were observed; the levels of sex hormones in serum were determined by ELISA;the expressions of E-cadherin, N-cadherin, Vimentin,Notch1 and Twist1 proteins were detected by immunohistochemistry and Western blot; the expressions of E-cadherin,N-cadherin, Vimentin, Notch1 and Twist1 were detected by Real-Time PCR. Results:Compared with the sham operation group,the levels of E2, P, FSH and LH in the serum of the model group were significantly increased(P<0.05),and the levels of N-cadherin, Vimentin, Notch1 and Twist1 proteins and mRNAs in the uterine tissue were significantly increased(P<0.01,P<0.05),while the levels of E-cadherin protein and mRNA were significantly decreased(P<0.01).Compared with the model group, the volume of ectopic lesions in the high and low dose groups of traditional Chinese medicine and the western medicine group was significantly reduced(P<0.05,P<0.01),the levels of E2, P, FSH and LH were significantly increased(P<0.05),and the levels of N-cadherin, Vimentin, Notch1 and Twist1 proteins and mRNAs in the uterine and ectopic lesion tissues were significantly decreased(P<0.01,P<0.05), while the levels of E-cadherin protein and mRNA were significantly increased(P<0.01). Conclusion: The Bushen Wenyang Huayu Formula can significantly inhibit the progression of EMs, and its mechanism may be related to the down-regulation of the expression of the Notch1/Twist1 signaling pathway, thereby regulating the EMT process of EMs.

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  • 收稿日期:2025-07-14
  • 最后修改日期:2025-10-18
  • 录用日期:2025-11-20
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