基于Wnt/β-catenin通路探究桃核承气汤对子宫内膜异位症大鼠的影响及作用机制

doi:10.3969/j.issn.1006-6233.2025.09.03

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摘要 目的: 基于Wnt/β-连环蛋白(β-catenin)通路探究桃核承气汤(THCQD)对子宫内膜异位症(EMs)大鼠的影响及作用机制。方法: 构建EMs大鼠模型,将大鼠随机分为EMs组(模型组)、L-THCQD组、M-THCQD组、H-THCQD组(THCQD低、中、高剂量组,分别灌胃1.89、3.78、7.56g/kg THCQD)、LiCl组(灌胃7.56g/kg THCQD和灌胃100mg/kg Wnt/β-catenin信号通路激活剂LiCl),每组各10只。另外选取10只大鼠为NC组(对照组),NC组与EMs组给予等体积氯化钠溶液。测量大鼠异位病灶体积和质量;HE染色观察大鼠异位子宫内膜组织病理变化;免疫组化法检测异位子宫内膜组织Ki67和血管内皮生长因子(VEGF)表达;TUNEL染色观察大鼠异位子宫内膜组织凋亡;ELISA检测大鼠血清炎性因子和性激素表达水平;Western blot检测大鼠异位子宫内膜组织Wnt/β-catenin通路以及凋亡相关蛋白表达。结果: 与NC组比较,EMs组大鼠异位子宫内膜组织病理损伤严重,Ki67、VEGF、IL-8、IL-6、IL-18、雌二醇(E2)、孕激素(P)、Wnt、β-catenin表达升高(P<0.05),促卵泡激素(FSH)、促黄体生成激素(LH)表达降低(P<0.05),凋亡率、Bcl-2、Bax表达无统计学意义(P>0.05);与EMs组比较,L-THCQD组、M-THCQD组、H-THCQD组大鼠异位子宫内膜组织病理损伤显著减轻,体积、质量、Ki67、VEGF、IL-8、IL-6、IL-18、E2、P、Bcl-2、Wnt、β-catenin表达显著降低(P<0.05),凋亡率、FSH、LH、Bax表达显著升高(P<0.05);与H-THCQD组比较,LiCl组大鼠异位子宫内膜组织病理损伤加重,体积、质量、Ki67、VEGF、IL-8、IL-6、IL-18、E2、P、Bcl-2、Wnt、β-catenin表达显著升高(P<0.05),凋亡率、FSH、LH、Bax表达显著降低(P<0.05)。结论: THCQD通过抑制炎症反应,促进异位子宫内膜组织凋亡,对EMs大鼠具有治疗作用,可能与抑制Wnt/β-catenin通路有关。

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关键词 ：子宫内膜异位症, 桃核承气汤, Wnt/β-连环蛋白, 作用机制

Abstract：Objective: To explore the effects of Taohe Chengqi decoction (THCQD) on endometriosis (EMs) rats through Wnt/β-catenin pathway and its mechanisms. Methods: An EMs rat model was constructed, and rats were randomly assigned into EMs group (Model group), L-THCQD (THCQD low dose) group, M-THCQD (THCQD medium dose) group, H-THCQD (THCQD high dose) group (The rats in these groups were fed 1.89, 3.78 and 7.56 g/kg THCQD, respectively), and LiCl group (orally administered 7.56 g/kg THCQD and orally administered 100mg/kg Wnt/β-catenin signaling pathway activator LiCl). Each group had 10 rats. Additionally, 10 rats were recruited as the NC group (Control group). The NC group and the EMs group were given equal volumes of sodium chloride solution. The volume and mass of ectopic lesions in rats were measured. HE staining was used to observe pathological changes in rat ectopic endometrial tissue. Immunohistochemistry was used to measure Ki67 and vascular endothelial growth factor (VEGF) in ectopic endometrial tissue. TUNEL staining was used to observe apoptosis in rat ectopic endometrial tissue. ELISA was performed to measure the inflammatory factors and sex hormones in serum. Western blot was performed to measure the Wnt/β-catenin pathway and apoptosis related proteins in rat ectopic endometrial tissue. Results: For the NC group, the EMs group showed severe pathological damage to ectopic endometrial tissue in rats, increased Ki67, VEGF, IL-8, IL-6, IL-18, estradiol (E2), progesterone (P), Wnt, and β-catenin (P<0.05), decrease follicle stimulating hormone (FSH) and luteinizing hormone (LH) (P<0.05), while the apoptosis rate, Bcl-2, and Bax no statistically conspicuous difference (P>0.05). For the EMs group, the L-THCQD group, M-THCQD group, and H-THCQD group showed significant reduction in pathological damage to rat ectopic endometrial tissue, significantly reduced volume, mass, Ki67, VEGF, IL-8, IL-6, IL-18, E2, P, Bcl-2, Wnt, and β-catenin (P<0.05), and significantly increased apoptosis rate and the expression of FSH, LH, and Bax (P<0.05). For the H-THCQD group, the LiCl group had aggravated pathological damage in rat ectopic endometrial tissue, significantly increased volume, mass, Ki67, VEGF, IL-8, IL-6, IL-18, E2, P, Bcl-2, Wnt, and β-catenin (P<0.05), and significantly reduced apoptosis rates and the expression of FSH, LH, and Bax (P<0.05). Conclusion: THCQD has therapeutic effects on EMs rats by inhibiting inflammatory responses and promoting apoptosis of ectopic endometrial tissue, which may be related to the inhibition of Wnt/β-catenin pathway.

Key words： Endometriosis Taohe Chengqi decoction Wnt/β-catenin Mechanism of action

基金资助:辽宁省科学技术计划项目,(编号:2023JH2/101700091)

通讯作者: 于月新

引用本文:

马金辉, 于月新, 张觅觅, 齐晓娟, 白雪, 肖玉红, 陈咏. 基于Wnt/β-catenin通路探究桃核承气汤对子宫内膜异位症大鼠的影响及作用机制[J]. 河北医学, 2025, 31(9): 1420-1427.
MA Jinhui, YU Yuexin, ZHANG Mimi, et al. Exploring the Effects of Taohe Chengqi Decoction on Endometriosis Rats through wnt/β-catenin Pathway and Its Mechanisms. HeBei Med, 2025, 31(9): 1420-1427.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.09.03 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I9/1420

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