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杨宗亮, 赵亮, 何永恒.白芍七物颗粒通过抑制PI3K/Akt/NF-κB信号通路修复溃疡性结肠炎肠道屏障的机制研究[J].湖南中医药大学学报,2026,46(7):1345-1354[点击复制] |
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| 白芍七物颗粒通过抑制PI3K/Akt/NF-κB信号通路修复溃疡性结肠炎肠道屏障的机制研究 |
| 杨宗亮,赵亮,何永恒 |
| (湖南中医药大学第二附属医院, 湖南 长沙 410005;湖南省中西医结合医院, 湖南 长沙 410006;湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨白芍七物颗粒对溃疡性结肠炎（UC）小鼠肠道屏障的修复作用，揭示其调控磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/核因子κB（NF-κB）信号通路的分子机制。方法 将60只C57BL/6小鼠随机分为正常组、模型组、LQ组（70 mg/mL白芍七物颗粒溶液）、HQ组（140 mg/mL白芍七物颗粒溶液）、阳性对照组（26 mg/mL美沙拉嗪溶液）、HQ+阳性对照组（140 mg/mL白芍七物颗粒溶液+26 mg/mL美沙拉嗪溶液），每组10只。除正常组外，其余各组采用3%葡聚糖硫酸钠（DSS）饮水7 d构建UC模型，造模同时各干预组给予相应药物灌胃，持续14 d。将构建成功的Caco-2细胞屏障模型随机分为空白组、模型组、白芍七物颗粒含药血清（YQ）组、阳性对照组、YQ+阳性对照组，各组给予相应培养基干预。通过疾病活动指数（DAI）评分、结肠长度及病理组织学评分评估小鼠疾病严重程度；采用Ussing Chamber系统检测结肠黏膜跨上皮电阻（TEER），荧光素钠渗透实验量化肠道屏障通透性；ELISA检测结肠组织白细胞介素（IL）-1β、单核细胞趋化蛋白-1（MCP-1）、IL-22水平；Western blot与RT-qPCR检测结肠组织及Caco-2细胞中PI3K/Akt/NF-κB通路关键分子（p-PI3K、PI3K、p-Akt、Akt、p-NF-κB p65、NF-κB p65）及紧密连接蛋白（Claudin-3、JAM-A、Cingulin）的蛋白与mRNA水平。结果 与模型组比较，LQ组、HQ组小鼠DAI评分、结肠黏膜病理评分、荧光素钠渗透量及结肠组织IL-1β、MCP-1水平降低（P<0.05），结肠长度延长（P<0.05），TEER值、结肠组织IL-22水平升高（P<0.05）；结肠组织中Claudin-3、JAM-A、Cingulin的蛋白与mRNA表达上调（P<0.05），p-PI3K、p-Akt、p-NF-κB p65的蛋白与mRNA表达下调（P<0.05）。与模型组比较，YQ组Caco-2细胞中Claudin-3、JAM-A、Cingulin的蛋白与mRNA表达上调（P<0.05），p-PI3K、p-Akt、p-NF-κB p65的蛋白与mRNA表达下调（P<0.05）。结论 白芍七物颗粒可能通过抑制PI3K/Akt/NF-κB信号通路，缓解肠道炎症，修复肠道损伤。 |
| 关键词: 溃疡性结肠炎|白芍七物颗粒|PI3K/Akt/NF-κB信号通路|肠道屏障|屏障损伤 |
| DOI：10.3969/j.issn.1674-070X.2026.07.005 |
| 投稿时间：2025-11-08 |
| 基金项目:〕湖南省自然科学基金项目（2026JJ81083）；长沙市自然科学基金项目（kq2403130）。 |
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| Mechanism of Baishao Qiwu Granule in repairing intestinal barrier of ulcerative colitis by inhibiting PI3K/Akt/NF-κB signaling pathway |
| YANG Zongliang, ZHAO Liang, HE Yongheng |
| (The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China;Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Changsha, Hunan 410006, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the reparative effects of Baishao Qiwu Granule (BSQWG) on intestinal barrier in mice with ulcerative colitis (UC), and to reveal its molecular mechanism by which it regulates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway. Methods Sixty C57BL/6 mice were randomly divided into normal group, model group, low-dose BSQWG group (LQ group) (70 mg/mL BSQWG solution), high-dose BSQWG group (HQ group) (140 mg/mL BSQWG solution), positive control group (26 mg/mL mesalazine solution), and HQ+positive control group (140 mg/mL BSQWG solution+26 mg/mL mesalazine solution), with 10 mice in each group. Except for the normal group, the other groups were given 3% dextran sodium sulfate (DSS) drinking water for 7 days to establish the UC model. Simultaneously with modeling, each intervention group received the corresponding drug by gavage for 14 consecutive days. A successfully established Caco-2 cell barrier model was randomly divided into blank group, model group, BSQWG containing serum group (YQ group), positive control group, and YQ+positive control group, each receiving the corresponding medium intervention. Disease severity of mice was assessed by disease activity index (DAI) score, colon length, and histopathological score. Transepithelial electrical resistance (TEER) of colonic mucosa was measured using an Ussing Chamber system, and intestinal barrier permeability was quantified by fluorescein sodium penetration assay. Levels of interleukin (IL)-1β, monocyte chemoattractant protein-1 (MCP-1), and IL-22 in colon tissues were determined by ELISA. Protein and mRNA levels of key molecules in the PI3K/Akt/NF-κB pathway (p-PI3K, PI3K, p-Akt, Akt, p-NF-κB p65, NF-κB p65) and tight junction proteins (Claudin-3, JAM-A, Cingulin) in colon tissues and Caco-2 cells were determined by Western blot and RT-qPCR. Results Compared with the model group, the LQ and HQ groups showed decreased DAI scores, colonic mucosal pathological scores, fluorescein sodium permeability, and colonic IL-1β and MCP-1 levels (P<0.05), increased colon length (P<0.05), elevated TEER values, and IL-22 levels in colon tissues (P<0.05), upregulated protein and mRNA expression of Claudin-3, JAM-A, and Cingulin in colon tissues (P<0.05), and downregulated protein and mRNA expression of p-PI3K, p-Akt, and p-NF-κB p65 (P<0.05). Compared with the model group, the YQ group exhibited upregulated protein and mRNA expression of Claudin-3, JAM-A, and Cingulin in Caco-2 cells (P<0.05), and downregulated protein and mRNA expression of p-PI3K, p-Akt, and p-NF-κB p65 (P<0.05). Conclusion BSQWG may alleviate intestinal inflammation and repair intestinal injury by inhibiting the PI3K/Akt/NF-κB signaling pathway. |
| Key words: ulcerative colitis|Baishao Qiwu Granule|PI3K/Akt/NF-κB signaling pathway|intestinal barrier|barrier injury |
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