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OA
Mechanism of Bushen Wenyang Huayu formula in regulating Notch1/Twist1 mediated epithelial-mesenchymal transition in the treatment of endometriosis
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(EMT)治疗子宫内膜异位症(EMs)的作用机制.方法 SD雌性大鼠随机分为假手术组、模型组、补肾温阳化瘀方高、低剂量组和地诺孕素组,采用自体移植法结合冰水浴构建肾阳虚型EMs大鼠模型,造模完成后补肾温阳化瘀方高、低剂量组分别给予补肾温阳化瘀方高、低剂量药液灌胃,地诺孕素组给予地诺孕素悬液灌胃,假手术组和模型组给予等体积蒸馏水灌胃,连续 21 d.观察子宫和异位灶重量、体积和粘连程度;ELISA测定血清中性激素的水平;免疫组织化学观察E-Cadherin、N-Cadherin、Vimentin及Notch1/Twist1 信号通路蛋白的定位与表达;Western blot及RT-qPCR检测E-Cadherin、N-Cadherin、Vimentin及Notch1/Twist1 信号通路的蛋白及mRNA表达情况.结果 与假手术组相比,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).与模型组相比,补肾温阳化瘀方高、低剂量组及地诺孕素组异位灶体积及重量明显减小(P<0.05,P<0.01),E2、P、FSH、LH水平显著降低(P<0.05),子宫及异位灶组织中N-Cadherin、Vimentin、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.
Objective To explore the mechanism of Bushen Wenyang Huayu formula in regulating the Notch1/Twist1 signaling pathway-mediated epithelial-mesenchymal transition(EMT)in the treatment of endometriosis.Methods SD female rats were randomly divided into Sham operation group,Model group,BWH-H group,BWH-L group,and Dienogest group.The EMs rat model of Kidney Yang Deficiency was constructed by autologous transplantation combined with ice water bath.After the modeling was completed,BWH-H group and BWH-L group were respectively given high and low-dose medicinal solutions of Bushen Wenyang Huayu formula by gavage.Dienoges group was given dienogest tablets by gavage,while Sham operation group and Model group were given an equal volume of distilled water by gavage for 21 consecutive days,weight,volume,and adhesion degree of ectopic lesions and uteri were observed.Serum levels of sex hormones were determined by enzyme-linked immunosorbent assay,E-Cadherin,N-Cadherin,Vimentin,Notch1,and Twist1 proteins were detected by immunohistochemistry and Western blot,and gene expression levels of E-Cadherin,N-Cadherin,Vimentin,Notch1,and Twist1 were detected by RT-qPCR.Results Serum levels of estradiol(E2),progesterone(P),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were significantly increased in Model group compared with Sham operation group(P<0.05).N-Cadherin,Vimentin,Notch1,and Twist1 protein and mRNA levels in uterine tissue were also significantly increased(P<0.01,P<0.05),while E-Cadherin protein and mRNA levels were significantly decreased(P<0.01).The volume and weigh of ectopic lesions was significantly reduced in BWH-H group and BWH-L group traditional Chinese medicine and Dienogest group,compared with Model group(P<0.05,P<0.01),while E2,P,FSH,and LH levels were significantly decreased(P<0.05),N-Cadherin,Vimentin,Notch1,and Twist1 protein and mRNA levels in the uterine and ectopic lesion tissues were significantly decreased(P<0.01,P<0.05),and E-Cadherin protein and mRNA levels were significantly increased(P<0.01).Conclusions Bushen Wenyang Huayu formula can significantly inhibit the progression of endometriosis,and its mechanism may be related to the down-regulation of the Notch1/Twist1 signaling pathway,thereby regulating the EMT process.
齐嘉泽;杨新宇;张丽美;孟鑫;马艺鸣;刘慧敏;陈景伟
河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091河北中医药大学,中西医结合研究所,河北省中西医结合肝肾病证研究重点实验室,石家庄 050091||河北省中西医结合生殖疾病协同创新中心,石家庄 050091
医药卫生
补肾温阳化瘀方子宫内膜异位症上皮-间质转化Notch1/Twist1 信号通路
Bushen Wenyang Huayu formulaendometriosisepithelial-mesenchymal transitionNotch1/Twist1 signaling pathway
《中国比较医学杂志》 2026 (1)
1-11,11
河北省自然科学基金资助项目(H2024423097,H2025423077)国家自然科学基金项目(82474558).
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