基于Wnt/β-catenin通路探讨自制丹归祛瘀丸联合针灸治疗子宫腺肌病小鼠的作用机制

doi:10.3969/j.issn.1006-6233.2025.03.07

摘要
图/表
参考文献
相关文章 (10)

全文: PDF (1770 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要 目的: 通过Wnt/β-catenin信号通路,探讨丹归祛瘀丸联合针灸对子宫腺肌病(adenomyosis,AM)小鼠的治疗作用。方法: 采用同种异体垂体移植法建立AM小鼠模型。将50只雌性ICR小鼠随机分为对照组(正常小鼠)、模型组(同种异体垂体诱导)、针灸组(针灸刺激三阴交穴)、丹归祛瘀丸组(3.25g/kg丹归祛瘀丸,灌胃)、联合组(3.25g/kg丹归祛瘀丸,灌胃＋针灸刺激三阴交穴),每组10只。在造模结束和治疗结束分别对各组小鼠进行热板痛阈实验,观察小鼠的行为学变化;离体检测各组小鼠子宫收缩频率和收缩波幅检测;采用H＆E进行小鼠子宫组织病理组织学分析并对各组病理组织进行评分;采用ELISA试剂盒检测子宫组织TNF-α、IL-1β、IL-6因子表达水平;采用Western Blot法检测Wnt/β-catenin通路Wnt3a、p-GSK-3β、p-β-catenin蛋白表达水平。结果: 相较于对照组,模型组小鼠子宫内膜与肌层腺体结构模糊不清,伴有大量炎性浸润,热板痛阈值、p-GSK-3β、p-β-catenin显著降低(P<0.05),子宫收缩频率与波幅、子宫内膜组织浸润评分、TNF-α、IL-1β、IL-6、Wnt3a显著升高(P<0.05);相较于模型组,单独的针灸组、丹归祛瘀丸组小鼠子宫内膜与肌层边界较为清晰,子宫内膜腺体浸润减轻,热板痛阈值、p-GSK-3β、p-β-catenin显著升高(P<0.05),子宫收缩频率与波幅、子宫内膜组织浸润评分、TNF-α、IL-1β、IL-6、Wnt3a显著降低(P<0.05);相较于单独的针灸组、丹归祛瘀丸组,联合组热板痛阈值、p-GSK-3β、p-β-catenin显著升高(P<0.05),子宫收缩频率与波幅、子宫内膜组织浸润评分、TNF-α、IL-1β、IL-6、Wnt3a显著降低(P<0.05)。结论: 丹归祛瘀丸联合针灸治疗AM小鼠的效果优于单独的电针组、丹归祛瘀丸组,其机制可能与抑制Wnt/β-catenin信号通路进而发挥抗炎、止痛效果有关。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章

关键词 ：子宫腺肌病, 丹归祛瘀丸, 针灸, Wnt/β-catenin通路

Abstract：Objective: To investigate the therapeutic effects of Dangui Quyu Pill combined with acupuncture on mice with adenomyosis (AM) through the Wnt/β-catenin signaling pathway. Methods: An AM mouse model was established using allogeneic pituitary transplantation. Fifty female ICR mice were randomly divided into five groups: control group (normal mice), model group (induced by allogeneic pituitary transplantation), acupuncture group (acupuncture stimulation at the Sanyinjiao point), Dangui Quyu Pill group (3.25g/kg Dangui Quyu Pill administered via gastric gavage), and combined group (3.25g/kg Dangui Quyu Pill administered via gastric gavage + acupuncture stimulation at the Sanyinjiao point), with 10 mice in each group. The hot plate pain threshold test was conducted at the end of modeling and treatment to observe behavioral changes. The frequency and amplitude of uterine contractions were measured in vitro. Histopathological analysis of uterine tissues was performed using H&E staining, and pathological scores were assigned. The expression levels of TNF-α, IL-1β, and IL-6 in uterine tissues were detected using ELISA kits. The protein expression levels of Wnt3a, p-GSK-3β, and p-β-catenin in the Wnt/β-catenin pathway were measured using Western Blot. Results: Compared with the control group, the model group exhibited blurred endometrial and myometrial glandular structures, significant inflammatory infiltration, decreased hot plate pain threshold, and reduced levels of p-GSK-3β and p-β-catenin (P<0.05). Conversely, uterine contraction frequency and amplitude, endometrial tissue infiltration scores, and the levels of TNF-α, IL-1β, IL-6, and Wnt3a were significantly increased (P<0.05). Compared with the model group, the acupuncture group and Dangui Quyu Pill group showed clearer boundaries between the endometrium and myometrium, reduced endometrial glandular infiltration, increased hot plate pain threshold, and elevated levels of p-GSK-3β and p-β-catenin (P<0.05). Additionally, uterine contraction frequency and amplitude, endometrial tissue infiltration scores, and the levels of TNF-α, IL-1β, IL-6, and Wnt3a were significantly decreased (P<0.05). Compared with the acupuncture group and Dangui Quyu Pill group, the combined group demonstrated further increases in the hot plate pain threshold and levels of p-GSK-3β and p-β-catenin (P<0.05), as well as further reductions in uterine contraction frequency and amplitude, endometrial tissue infiltration scores, and the levels of TNF-α, IL-1β, IL-6, and Wnt3a (P<0.05). Conclusion: The combination of Dangui Quyu Pill and acupuncture exhibits superior therapeutic effects on AM mice compared to either treatment alone. The underlying mechanism may involve the inhibition of the Wnt/β-catenin signaling pathway, thereby exerting anti-inflammatory and analgesic effects.

Key words： Adenomyosis Dangui quyu pill Acupuncture Wnt/β-catenin pathway

基金资助:河北省中医药管理局科研计划项目,(编号:2023250)

通讯作者: 张士表

引用本文:

李世大, 朱芳芳, 翟倩, 陈秀英, 张士表. 基于Wnt/β-catenin通路探讨自制丹归祛瘀丸联合针灸治疗子宫腺肌病小鼠的作用机制[J]. 河北医学, 2025, 31(3): 390-395.
LI Shida, ZHU Fangfang, ZHAI Qian, et al. An Investigation of the Mechanism of Self-Made Dangui Quyu Pill Combined with Acupuncture in Treating Mice with Adenomyosis Based on the Wnt/β-Catenin Pathway. HeBei Med, 2025, 31(3): 390-395.

链接本文:

http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.03.07 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I3/390

[1] Moawad G,Fruscalzo A,Youssef Y,et al.Adenomyosis:an updated review on diagnosis and classification[J].Clin Med,2023,12(14):4828.
[2] 潘丹,郎伯旭,林巧.针刺联合隔药饼灸周期调治肾虚血瘀型子宫腺肌症疗效观察[J].上海针灸杂志,2020,39(1):42-46.
[3] 李世大,陈秀英,张士表.丹归祛瘀丸联合醋酸亮丙瑞林治疗子宫腺肌病的临床观察[J].中国民间疗法,2024,32(1):80-82.
[4] 徐晓霞,应翩,张静.裘氏内异方对子宫腺肌病模型小鼠MAPK/ERK1/2信号通路的影响及机制研究[J].新中医,2023,55(13):22-28.
[5] Vercellini P,Viganò P,Bandini V,et al.Association of endometriosis and adenomyosis with pregnancy and infertility[J].Fertil Steril,2023,119(5):727-740.
[6] 李彧,程雯,李森,等.俞氏化瘀止血方联合左炔诺孕酮宫内缓释系统治疗子宫腺肌病的前瞻性、随机、双盲、安慰剂对照研究[J].海军军医大学学报,2024,45(9):1069-1076.
[7] 黄涛.针药结合分期治疗子宫内膜异位/子宫腺肌症20例[J].中国针灸,2018,38(5):490-492.
[8] Shi J,Xu Q,Yu S,Zhang T.Perturbations of the endometrial immune microenvironment in endometriosis and adenomyosis:their impact on reproduction and pregnancy[J].Semin Immunopathol,2025,47(1):16.
[9] Bourdon M,Santulli P,Jeljeli M,et al.Immunological changes associated with adenomyosis:a systematic review[J].Hum Reprod Update,2021,27(1):108-129.
[10] Li M,Li T,Jin T,et al.Abnormal activation of the Wnt3a/β-catenin signaling pathway promotes the expression of T-box transcription factor 3(TBX3) and the epithelial-mesenchymal transition pathway to mediate the occurrence of adenomyosis[J].Mol Biol Rep,2023,50(12):9935-9950.
[11] Kobayashi H.Molecular targets for nonhormonal treatment based on a multistep process of adenomyosis development[J].Reprod Sci,2023,30(3):743-760.
[12] Xu X,Cai B,Liu Y,et al.MIR503HG silencing promotes endometrial stromal cell progression and metastasis and suppresses apoptosis in adenomyosis by activating the Wnt/β-catenin pathway via targeting miR-191[J].Exp Ther Med,2023,25(3):117.
[13] Chen R,Li M,Ding M.Optogenetic stimulation of the "Zusanli" acupoint alleviates inflammatory pain through active Wnt/β-Catenin and MAPK signaling pathway in rats[J].Heliyon,2024,10(21):39992.