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喻舟, 佘畅, 石佳, 王超.基于NF-κB/NLRP3通路探讨隔药饼灸对腹泻型肠易激综合征大鼠水通道蛋白的影响[J].湖南中医药大学学报,2026,46(4):715-724[点击复制] |
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| 基于NF-κB/NLRP3通路探讨隔药饼灸对腹泻型肠易激综合征大鼠水通道蛋白的影响 |
| 喻舟,佘畅,石佳,王超 |
| (湖南中医药大学针灸推拿与康复学院, 湖南 长沙 410208;长沙市中医医院(长沙市第八医院), 湖南 长沙 410002) |
| 摘要: |
| 目的 探究隔药饼灸对腹泻型肠易激综合征大鼠水通道蛋白的影响及其作用机制。方法 将32只大鼠随机分为空白组、模型组、隔药饼灸组和吡咯烷二硫代氨基甲酸酯（PDTC）组，每组8只。除空白组外，其余各组均采用番泻叶水煎液灌胃联合束缚应激法构建腹泻型肠易激综合征（IBS-D）大鼠模型，连续14 d。造模成功后，隔药饼灸组于“肝俞、脾俞、足三里”及“章门、期门、足三里”两组穴位隔日交替施灸，每穴灸5壮，每日1次，持续14 d;PDTC组腹腔注射核因子κB(NF-κB)抑制剂PDTC溶液（100 mg/kg），每日1次，持续14 d。检测大鼠体质量、粪便含水量及腹部撤回反射（AWR）评分；HE染色观察结肠黏膜组织形态；ELISA检测血浆D-乳酸含量；采用qRT-PCR及免疫组织化学法检测结肠组织水通道蛋白（AQP1、AQP3、AQP8）、转化生长因子-β(TGF-β)、NF-κB p65、Nod样受体蛋白3(NLRP3)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的m RNA表达及阳性细胞率；采用Western blot检测NF-κB/NLRP3炎症轴核心蛋白NF-κB p65、NLRP3及关键水通道蛋白AQP1、AQP3、AQP8的相对表达量。结果 与空白组比较，模型组大鼠体质量显著降低（P<0.01），粪便含水量、AWR评分及血浆D-乳酸含量显著升高（P<0.01）；结肠组织可见明显炎症细胞浸润及肌纤维萎缩；AQP1、AQP3、AQP8、TGF-β的mRNA表达与阳性细胞率显著降低（P<0.01）,NF-κB p65、NLRP3、IL-1β、TNF-α的m RNA表达与阳性细胞率显著升高（P<0.01）;AQP1、AQP3、AQP8蛋白相对表达量显著降低（P<0.01）,NF-κB p65、NLRP3蛋白相对表达量显著升高（P<0.01）。干预后，与模型组比较，隔药饼灸组和PDTC组体质量显著回升（P<0.01），粪便含水量、AWR评分及血浆D-乳酸含量降低（P<0.05,P<0.01）；结肠病理损伤减轻；AQP1、AQP3、AQP8及TGF-β的mRNA表达与阳性细胞率升高（P<0.05,P<0.01）,NF-κB p65、NLRP3、IL-1β及TNF-α的mRNA表达与阳性细胞率显著降低（P<0.01）;AQP1、AQP3、AQP8蛋白相对表达量升高（P<0.05,P<0.01）,NF-κB p65、NLRP3蛋白相对表达量降低（P<0.05,P<0.01）。结论 隔药饼灸能有效改善IBS-D大鼠的腹泻、内脏高敏感及肠黏膜通透性，其作用机制可能与下调NF-κB/NLRP3通路相关分子及促炎因子（IL-1β、TNF-α）、上调水通道蛋白（AQP1、AQP3、AQP8）的表达有关。 |
| 关键词: 腹泻型肠易激综合征|隔药饼灸|NF-κB/NLRP3通路|水通道蛋白|肠黏膜通透性|肠道炎症|中医外治法 |
| DOI：10.3969/j.issn.1674-070X.2026.04.008 |
| 投稿时间：2025-10-29 |
| 基金项目:湖南省自然科学基金青年基金项目(2024JJ6350,2021JJ40404);湖南省中医药科研计划项目(B2023108);全国中医药研究生教育研究课题(YJS-YB-2023-29);第七批全国老中医药专家学术经验继承工作项目;湖南中医药大学研究生创新课题项目(2024CX163) |
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| Effects of moxibustion on herbal cake on aquaporins in rats with diarrhea-predominant irritable bowel syndrome based on the NF-κB/NLRP3 pathway |
| YU Zhou, SHE Chang, SHI Jia, WANG Chao |
| (School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, Hunan 410002, China) |
| Abstract: |
| Objective To investigate the effects of moxibustion on herbal cake(MHC) on aquaporins in rats with diarrheapredominant irritable bowel syndrome(IBS-D) and to explore its underlying mechanism of action. Methods Thirty-two rats were randomized into blank, model, MHC, and pyrrolidine dithiocarbamate(PDTC) groups, with 8 rats in each group. Except for the blank group, all rats were subjected to intragastric administration of senna leaf decoction combined with restraint stress for 14 consecutive days to establish the IBS-D model. After successful modeling, the MHC group received moxibustion on two alternating acupoint combinations every other day: "Ganshu(BL18), Pishu(BL20), and Zusanli(ST36)" and "Zhangmen(LR13), Qimen(LR14), and Zusanli(ST36)". Five moxa cones were applied at each acupoint once daily for 14 days. The PDTC group received intraperitoneal injection of the NF-κB inhibitor PDTC(100 mg/kg) once daily for 14 days. Body weight, fecal water content, and abdominal withdrawal reflex(AWR) scores were measured. HE staining was used to observe the colonic mucosal morphology. ELISA was used to test the plasma D-lactate levels. qRT-PCR and immunohistochemistry were applied to measure the mRNA expression and positive cell rates of aquaporins(AQP1, AQP3, AQP8), transforming growth factor-β(TGF-β), NF-κB p65, Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in colonic tissues. Western blot was used to determine the relative protein expression of the core proteins in the NF-κB/NLRP3 inflammatory axis, namely NF-κB p65 and NLRP3, as well as the key aquaporins AQP1, AQP3, and AQP8. Results Compared with the blank group, the model group showed significantly decreased body weight(P<0.01), significantly increased fecal water content, AWR scores, and plasma D-lactate levels(P<0.01). Histological examination revealed obvious inflammatory cell infiltration and muscle fiber atrophy in colonic tissues. The mRNA expression levels and positive cell rates of AQP1, AQP3, AQP8, and TGF-β were significantly decreased(P<0.01), whereas those of NF-κB p65, NLRP3, IL-1β,and TNF-α were significantly increased(P<0.01). In addition, the relative protein expression levels of AQP1, AQP3, and AQP8 were significantly decreased(P<0.01), while those of NF-κB p65 and NLRP3 were significantly increased(P<0.01). After intervention,compared with the model group, both the MHC and PDTC groups exhibited significantly increased body weight(P<0.01), decreased fecal water content, AWR scores, and plasma D-lactate levels(P<0.05, P<0.01), and alleviated colonic pathological injury. In addition, the mRNA expression levels and positive cell rates of AQP1, AQP3, AQP8, and TGF-β were increased(P<0.05, P<0.01),whereas those of NF-κB p65, NLRP3, IL-1β, and TNF-α were significantly decreased(P<0.01). The relative protein expression of AQP1, AQP3, and AQP8 was increased(P<0.05, P<0.01), whereas that of NF-κB p65 and NLRP3 was decreased(P<0.05, P<0.01).Conclusion MHC can effectively improve diarrhea, visceral hypersensitivity, and abnormal intestinal mucosal permeability in IBS-D rats. Its mechanism of action may be associated with downregulation of NF-κB/NLRP3 pathway-related molecules and proinflammatory cytokines(IL-1β and TNF-α), along with upregulation of aquaporins(AQP1, AQP3, and AQP8). |
| Key words: diarrhea-predominant irritable bowel syndrome|moxibustion on herbal cake|NF-κB/NLRP3 pathway|aquaporins|intestinal mucosal permeability|intestinal inflammation|TCM external therapy |
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