南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (2): 293-300.doi: 10.12122/j.issn.1673-4254.2026.02.07

• • 上一篇    

化瘀通便汤通过抑制PI3K/Akt信号通路促进慢传输型便秘大鼠肠道Cajal间质细胞的胞葬作用

邱佳惠1(), 陈萌2(), 满如3, 陈鑫1, 邱东瑞1, 常启同1, 马洪玉1   

  1. 1.辽宁中医药大学,第三临床学院,辽宁 沈阳 110847
    3.辽宁中医药大学,护理学院,辽宁 沈阳 110847
    2.辽宁中医药大学附属第三医院,辽宁 沈阳 110003
  • 收稿日期:2025-07-16 出版日期:2026-02-20 发布日期:2026-03-10
  • 通讯作者: 陈萌 E-mail:3010057273@qq.com;187362783@qq.com
  • 作者简介:邱佳惠,在读硕士研究生,E-mail: 3010057273@qq.com
  • 基金资助:
    国家自然科学基金青年科学基金(81804094);辽宁省教育厅(JYTMS20231814);辽宁省教育厅高校基本科研项目储备项目(2024-JYTCB-001)

Huayu Tongbian Decoction promotes efferocytosis of interstitial Cajal cells in rats with slow transit constipation by inhibiting the PI3K/Akt signaling pathway

Jiahui QIU1(), Meng CHEN2(), Ru MAN3, Xin CHEN1, Dongrui QIU1, Qitong CHANG1, Hongyu MA1   

  1. 1.Third Clinical College, Shenyang 110003, China
    3.College of Nursing, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China, Shenyang 110003, China
    2.Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110003, China
  • Received:2025-07-16 Online:2026-02-20 Published:2026-03-10
  • Contact: Meng CHEN E-mail:3010057273@qq.com;187362783@qq.com
  • Supported by:
    Natural Science Foundation for the Youth (NSFY) of China(81804094)

摘要:

目的 基于磷脂酰肌醇-3-激酶蛋白激酶B(PI3K/Akt)信号通路,通过对慢传输型便秘(STC)大鼠结肠Cajal间质细胞(ICCs)胞葬过程的变化进行评价,探索化瘀通便汤对慢传输型便秘的作用机制。 方法 取SD大鼠采用盐酸洛哌丁胺混悬液灌胃法制备STC模型,随机分为模型组、化瘀通便汤中药低剂量组、化瘀通便汤中药中剂量组、化瘀通便汤中药高剂量组、阳性药物(莫沙必利)组,每组12只,另取12只SD大鼠灌胃等剂量生理盐水设为空白组。测量各组大鼠首次黑便时间、粪便含水率、肠道推进率;通过透射电镜观察分析Cajal间质细胞超微结构,计算线粒体空泡率;免疫荧光实验检测各组大鼠巨噬细胞吞噬率;HE染色检测各组大鼠结肠病理形态;免疫组织化学(IHC)染色检测各组大鼠结肠组织酪氨酸蛋白激酶受体(c-Kit)表达水平;Western blotting法检测大鼠结肠c-Kit、整联蛋白相关蛋白(CD47)、PI3K、Akt蛋白含量,分析各项指标与胞葬作用的相关性。 结果 与空白组比较,模型组大鼠出现典型的便秘症状,Cajal间质细胞超微结构明显损坏,大鼠结肠黏膜出现明显病理损伤,首次黑便时间、线粒体空泡率、CD47、p-PI3K/PI3K、p-Akt/Akt蛋白表达水平明显升高(P<0.01),粪便含水率、肠道推进率、c-Kit蛋白表达水平明显降低(P<0.01),吞噬率两组无明显差异。与模型组比较,化瘀通便汤中药各剂量组大鼠Cajal间质细胞超微结构形态基本正常,大鼠结肠黏膜病理损伤明显减轻,粪便含水率、肠道推进率、吞噬率、c-Kit蛋白表达明显升高(P<0.05),首次黑便时间、线粒体空泡率、CD47、p-PI3K/PI3K、p-Akt/Akt蛋白含量均降低(P<0.05),其中,化瘀通便汤中药高剂量组结果最为显著(P<0.01)。 结论 化瘀通便汤可能通过抑制PI3K、Akt的磷酸化,下调CD47蛋白表达,提高巨噬细胞吞噬率,从而促进Cajal间质细胞的胞葬过程,发挥对慢传输型便秘的治疗作用。

关键词: 化瘀通便汤, 胞葬作用, 慢传输型便秘, PI3K/Akt信号通路, Cajal间质细胞

Abstract:

Objective To explore the mechanism of Huayu Tongbian Decoction (HYTBD) for relieving slow transit constipation (STC) in rats. Methods Sixty SD rat models of STC induced by intragastric administration of loperamide hydrochloride suspension were randomized equally into 5 groups for treatment with daily gavage with saline (STC model group), low-, medium-, or high-dose HYTBD, or mosapride (positive control group), with another 12 normal rats receiving saline gavage as the blank control group. The first black stool time, fecal water content and intestinal propulsion rate of the rats were measured, and the ultrastructure of interstitial Cajal cells (ICCs) was observed using transmission electron microscopy to calculate the mitochondrial vacuolar rate. The phagocytosis rate of macrophages was detected using immunofluorescence assay, and colonic pathologies were examined using HE staining. The colonic expression levels of c-Kit, CD47, PI3K and Akt were detected with immunohistochemistry or Western Blotting, and their correlations with efferocytosis were analyzed. Results The rat models of STC showed significant ultrastructural damage of the ICCs with increased first black stool time, mitochondrial vacuolar rate, and colonic expression levels of CD47, p-PI3K/PI3K and p-Akt/Akt proteins, lowered fecal water content, intestinal propulsion rate and c-Kit expression level, without significant changes in phagocytic rate. Treatment with HYTBD, especially at the high dose, significantly increased fecal water content, intestinal propulsion rate, phagocytosis rate and colonic c-Kit expression, and decreased the first black stool time, mitochondrial vacuolar rate, and colonic expressions of CD47, p-PI3K/PI3K and p-Akt/Akt in the mouse models. Conclusion HYTBD improves STC in rats possibly by down-regulating colonic CD47 expression and improving macrophage phagocytosis rate via inhibiting PI3K and Akt phosphorylation, thereby promoting efferocytosis of the ICCs.

Key words: Huayu Tongbian Decoction, efferocytosis, slow transit constipation, PI3K/Akt signaling pathway, interstitial Cajal cells