| 摘要: |
| 目的:基于Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-κB(NF-κB)信号通路研究灭幽汤发酵液对幽门螺杆菌感染相关性胃炎小鼠的治疗作用及机制。方法:44只雄性SPF级BALB/c小鼠，随机取34只，采用幽门螺杆菌菌液灌胃(隔天1次，共6次)制备幽门螺杆菌感染模型，其余10只为对照组；于最后一次灌胃后14天，各取2只小鼠行快速尿素酶实验和Giemsa染色，确认造模成功后，随机分为模型组、灭幽汤组、发酵液组和西药组，共4组，每组8只，给予相应药物治疗14 d。采用快速尿素酶实验检测幽门螺杆菌根除率，Giemsa及HE染色观察幽门螺杆菌定植及炎症浸润情况，并用免疫组化及实时荧光定量PCR检测胃组织中TLR4、MyD88和NF-κB的蛋白及mRNA表达水平，ELISA检测血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-8水平。结果:与对照组比较，模型组小鼠胃黏膜可见大量炎性细胞浸润及幽门螺杆菌，TLR4、Myd88和NF-κB的蛋白与mRNA表达水平及血清TNF-α、IL-8含量明显升高(P ＜0.05)。与模型组比较，灭幽汤组、发酵液组及西药组胃黏膜炎症减轻，相关基因蛋白与mRNA的表达水平及血清TNF-α、IL-8含量均降低(P ＜0.05)。与灭幽汤组比较，发酵液组及西药组各项检测指标均降低(P ＜0.05)。结论:灭幽汤及其发酵液均可抑制幽门螺杆菌定植，减轻胃黏膜炎症，且发酵液的疗效更佳，其治疗机制与抑制TLR4/MyD88/NF-κB信号通路有关。 |
| 关键词: 幽门螺杆菌 胃炎 灭幽汤发酵液 TLR4/MyD88/NF-κB通路 |
| DOI：10.3969/j.issn.1007-6948.2025.05.024 |
| 投稿时间：2025-04-20 |
| 基金项目:湖南省自然科学基金面上项目(2024JJ5310)；湖南省教育厅科研项目(19A375)；中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目(23PTKF1002) |
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| Effect of the fermented broth of Mieyou decoction on TLR4/MyD88/NF-κB signaling pathway in mice with Helicobacter pylori infection-related gastritis |
| ZHANG Xu-yuan,GUO Xuan |
| School of Integrated Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha41000, China |
| Abstract: |
| Objective To investigate the therapeutic effect and mechanism of the fermentation broth of Mieyou decoction on mice with Helicobacter pylori infusion-associated gastritis based on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. Methods Forty-four mice were marked as the blank group (10 mice) and the model group (34 mice). After 7 days of adaptive rearing, Helicobacter pylori bacterial liquid was gavaged once every other day for a total of 6 times. After 14 days of conventional feeding, 2 mice from each group were selected for the Rapid Urease Test (RUT) and Giemsa staining to detect whether the modeling was successful. The remaining mice were divided into the control group, the model group, the Mieyou decoction group, the fermentation broth group and the Western medicine group, with 8 mice in each group. The drug intervention lasted for 14 days. The mice were sacrificed to obtain gastric tissues, and RUT was used to detect the H.pylori eradication rate of the mice. Giemsa and HE staining were used to observe the colonization and inflammatory infiltration of H.pylori in mice. The protein and mRNA levels of TLR4, MyD88 and NF-κB in mouse gastric tissues were detected by IHC method and real-time fluorescence quantitative PCR. The expression changes of TNF-α and IL-8 in the serum of mice were evaluated by ELISA. Results Compared with the blank group, a large number of inflammatory cell infiltrations and the presence of Helicobacter pylori could be observed in the gastric mucosa of mice in the model group. The protein and mRNA levels of TLR4, Myd88 and NF-κB, as well as the serum contents of TNF-α and IL-8, were significantly increased (P <0.05). Compared with the model group, the gastric mucosal inflammation of mice in the Mieyou decoction group, the fermentation broth group and the Western medicine group improved, and the expression levels of each protein and mRNA as well as the serum contents of TNF-α and IL-8 all decreased (P <0.05). Compared with the Mieyou decoction group, the gastric mucosal inflammation of mice in the fermentation broth group and the Western medicine group improved, and the levels of expression of each protein and mRNA as well as the serum contents of TNF-α and IL-8 decreased (P <0.05). Conclusion Both the Mieyou decoction and its fermentation broth can inhibit the colonization of Helicobacter pylori, reduce gastric mucosal inflammation, and the fermentation broth has better therapeutic effects. Its therapeutic mechanism is related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway. |
| Key words: Helicobacter pylori gastritis Mieyou decoction TLR4/MyD88/NF-κB signaling pathway |
