中华中医药学刊

基于TLR5/NF-κB信号通路及肠道菌群探讨香连丸治疗幽门螺杆菌胃炎的作用机制

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张孟维 ¹^,² , 黄超群 ³^,⁴ , 萧闵 ³^,⁵ , 张念 ² , 周盾 ² , 张霖 ⁶ , 胡运莲 ³^,⁴^,⁷

中华中医药学刊 | 国家项目点击 2026,44(7): 124-130

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中华中医药学刊 |国家项目点击 2026 , 44 (7) : 124 -130

基于TLR5/NF-κB信号通路及肠道菌群探讨香连丸治疗幽门螺杆菌胃炎的作用机制

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张孟维¹^,², 黄超群³^,⁴, 萧闵³^,⁵, 张念², 周盾², 张霖⁶, 胡运莲³^,⁴^,⁷

作者信息

^1.湖北中医药大学中医学院，湖北　武汉　430065

^2.武汉市中西医结合医院，湖北　武汉　430033

^3.湖北时珍实验室，湖北　武汉　430060

^4.湖北中医药大学附属医院（湖北省中医院），湖北　武汉　430073

^5.湖北中医药大学实验动物中心，湖北　武汉　430065

^6.襄阳市中医医院（襄阳市中医药研究所），湖北　襄阳　441000

^7.湖北中医药大学第一临床学院，湖北　武汉　430061

通讯作者:

张霖（1981-），男，湖北潜江人，副主任医师，硕士研究生导师，博士，研究方向：中西医结合治疗消化疾病。E-mail：zhanglin_011@163.com。

胡运莲（1964-），女，湖北宜昌人，主任医师，博士研究生导师，博士，研究方向：中西医结合治疗消化疾病。E-mail：843214365@qq.com。

作者简介:

张孟维（1990-），女，湖北仙桃人，博士在读，研究方向：中西医结合治疗消化疾病。

Mechanism of Xianglian Pills (香连丸) in Treating Helicobacter pylori-Associated Gastritis Based on TLR5/NF-κB Signaling Pathway and Gut Microbiota

Mengwei ZHANG¹^,², Chaoqun HUANG³^,⁴, Min XIAO³^,⁵, Nian ZHANG², Dun ZHOU², Lin ZHANG⁶, Yunlian HU³^,⁴^,⁷

Affiliations

^1.College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China

^2.Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430033, Hubei, China

^3.Hubei Shizhen Laboratory, Wuhan 430060, Hubei, China

^4.Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan 430073, Hubei, China

^5.Laboratory Animal Center, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China

^6.Xiangyang Hospital of Traditional Chinese Medicine (Xiangyang Institute of TCM), Xiangyang 441000, Hubei, China

^7.First Clinical College, Hubei University of Chinese Medicine, Wuhan 430061, Hubei, China

出版时间: 2026-07-10 doi: 10.13193/j.issn.1673-7717.2026.07.023

文章导航

摘要

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目的

基于Toll样受体5（Toll-like receptor 5，TLR5）/核因子κB（nuclear factor-kappa B，NF-κB）信号通路和肠道菌群，探讨不同剂量香连丸对幽门螺杆菌胃炎（helicobacter pylori-associated gastritis，HPAG）脾胃湿热证大鼠的作用机制。

方法

将60只SPF级健康雄性Wistar大鼠适应性喂养1周，采用随机数字表法分为空白组（n=10）和干预组（n=50），干预组采用复合因素造模构建HPAG脾胃湿热证大鼠模型，造模成功后，将干预组分为模型组、香连丸低剂量组（0.54 g·kg^-1）、香连丸中剂量组（1.08 g·kg^-1）、香连丸高剂量组（2.16 g·kg^-1）及西药组，每组10只，空白组、模型组给予等体积蒸馏水灌胃，连续21 d。观察期内，每周测量大鼠体质量；给药结束后，采集大鼠新鲜粪便，采用16S rRNA测序技术，研究各组肠道菌群的差异和变化；采用苏木素-伊红（hematoxylin-eosin，HE）染色观察大鼠胃黏膜组织病理学改变；采用吉姆萨（Giemsa）染色观察大鼠胃黏膜幽门螺杆菌情况；采用酶联免疫吸附测定法（enzyme-linked immunosorbent assay，ELISA）检测大鼠血清肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（inter-leukin-6，IL-6）的水平；采用蛋白免疫印迹法（Western blot）检测大鼠TLR5、TNF受体相关因子6（TNF receptor-related factor 6，TRAF6）、转化生长因子β活化激酶1（transforming growth factor β-activated kinase 1，TAK1）、核因子κB抑制物激酶α（nuclear factor κB inhibitor kinase α，IKKα）、NF-κB、髓样分化因子88（myeloid differentiation factor 88，MyD88）、核因子κB p50蛋白、核因子κB p65蛋白表达水平。

结果

与空白组相比，模型组大鼠平均体质量下降（P<0.01），湿热症状明显（P<0.01）；胃黏膜上皮细胞排列紊乱，部分胃腺体呈萎缩或异型性，黏膜下可见大量炎细胞浸润；可见大量的呈弯曲状或短杆状紫蓝色成簇的幽门螺杆菌；血清TNF-α、IL-6含量显著升高（P<0.01）；TLR5、TRAF6、TAK1、IKKα、NF-κB、MyD88、p50、p65蛋白表达增加（P<0.05）；肠道菌群紊乱（P<0.05）。与模型组相比，香连丸低、中、高剂量组平均体质量及湿热证候改善（P<0.05），大鼠胃黏膜上皮细胞排列相对整齐，腺体萎缩及异型性减少，黏膜下炎细胞浸润明显减少；血清TNF-α、IL-6水平明显下调（P<0.01）；TLR5、TRAF6、TAK1、IKKα、NF-κB、MyD88、p50、p65蛋白表达减少（P<0.05）；肠道有益菌增加（P<0.05）。

结论

香连丸可以显著改善HPAG脾胃湿热证大鼠胃黏膜损伤，其具体机制可能与调节TLR5/NF-κB信号通路和肠道菌群有关。

关键词

幽门螺杆菌胃炎 / 脾胃湿热证 / 香连丸 / 肠道菌群 / Toll样受体5 / 核因子-κB

Abstract

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Objective

Based on Toll-like receptor 5 (TLR5)/nuclear factor-kappa B (NF-κB) signaling pathway and gut microbiota, the mechanism of different doses of Xianglian Pills (香连丸) on Helicobacter pylori-associated gastritis (HPAG) rats with damp-heat in spleen-stomach syndrome was explored.

Methods

Sixty SPF healthy male Wistar rats were fed adaptively for one week and divided into blank group (10 rats) and intervention group (50 rats) by random number table method. The intervention group utilized a multi-factor modeling approach to construct a rat model of HPAG with damp-heat in spleen-stomach syndrome. After successful modeling, the intervention group was further divided into model group, Xianglian Pills low-dose group (0.54 g·kg^-1), Xianglian Pills medium-dose group (1.08 g·kg^-1), Xianglian Pills high-dose group (2.16 g·kg^-1) and western medicine group, with 10 rats in each group. Blank group and model group were given the equal volume of distilled water for 21 consecutive days. During the observation period, the body weight of the rats was measured weekly. After the administration, the fresh feces of the rats were collected and 16S rRNA sequencing technology was used to investigate the differences and changes in gut microbiota among the groups. Hematoxylin-eosin (HE) staining was employed to examine the histopathological changes of gastric mucosa in the rats. Giemsa staining was used to detect Helicobacter pylori in gastric mucosa of the rats. The serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in the rats were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to determine the protein levels of TLR5, TNF receptor-related factor 6 (TRAF6), transforming growth factor β-activated kinase 1 (TAK1), nuclear factor κB inhibitor kinase α(IKKα), NF-κB, myeloid differentiation factor 88 (MyD88), NF-κB p50 protein and NF-κB p65 protein in the rats.

Results

Compared with those in the blank group, the average body weight of the rats in the model group decreased significantly (P<0.01), and the symptoms of damp-heat in spleen-stomach syndrome were obvious (P<0.01). The gastric mucosal epithelial cells exhibited disordered arrangement, with partial gastric glands showing atrophy or atypia. A large number of inflammatory cells were infiltrated the submucosa. Additionally, a significant number of curved or short rod-shaped, purple-blue clusters of Helicobacter pylori were visible. The serum levels of TNF-α and IL-6 were significantly increased (P<0.01). The protein expression levels of TLR5, TRAF6, TAK1, IKKα, NF-κB, MyD88, NF-κB p50 protein and NF-κB p65 protein were elevated (P<0.05). Furthermore, the gut microbiota dysbiosis was observed (P<0.05). Compared with those of the model group, the average body weight and damp-heat syndrome of the low, medium and high groups of Xianglian Pills were improved (P<0.05). The gastric mucosal epithelial cells were arranged in a relatively orderly way, with reduced glandular atrophy and atypia, as well as a significant decrease in inflammatory cell infiltration in the submucosa. The serum levels of TNF-α and IL-6 were significantly down-regulated (P<0.01). The protein expression levels of TLR5, TRAF6, TAK1, IKKα, NF-κB, MyD88, NF-κB p50 protein and NF-κB p65 protein were reduced (P<0.05). Additionally, the abundance of beneficial gut bacteria increased (P<0.05).

Conclusion

-Xianglian Pills can significantly improve gastric mucosal injury in HPAG rats with damp-heat in spleen-stomach syndrome, and its specific mechanism may be related to the regulation of TLR5/NF-κB signaling pathway and gut microbiota.

Key words

Helicobacter pylori-associated gastritis / damp-heat in spleen-stomach syndrome / Xianglian Pills (香连丸) / gut microbiota / Toll-like receptor 5 / nuclear factor-kappa B

引用本文

张孟维, 黄超群, 萧闵, 张念, 周盾, 张霖, 胡运莲. 基于TLR5/NF-κB信号通路及肠道菌群探讨香连丸治疗幽门螺杆菌胃炎的作用机制. 中华中医药学刊, 2026 , 44 (7) : 124 -130 . DOI: 10.13193/j.issn.1673-7717.2026.07.023

Mengwei ZHANG, Chaoqun HUANG, Min XIAO, Nian ZHANG, Dun ZHOU, Lin ZHANG, Yunlian HU. Mechanism of Xianglian Pills (香连丸) in Treating Helicobacter pylori-Associated Gastritis Based on TLR5/NF-κB Signaling Pathway and Gut Microbiota[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (7) : 124 -130 . DOI: 10.13193/j.issn.1673-7717.2026.07.023

基金

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国家自然科学基金面上项目(82374205)
湖北省科学技术厅自然科学基金创新发展联合基金项目(2022CFD116)
湖北省时珍人才工程科研项目(鄂卫函〔2024〕256号)
武汉市中医药科研项目(WZ24A35)

参考文献

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文献

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参考文献引证文献

排序方式：

[1]

中华医学会消化病学分会, 中华医学会消化病学分会消化系统肿瘤协作组, 房静远. 中国慢性胃炎诊治指南(2022年, 上海)[J]. 胃肠病学, 2023, 28(3): 149-180.

[2]

中华医学会消化病学分会幽门螺杆菌学组. 第六次全国幽门螺杆菌感染处理共识报告(非根除治疗部分)[J]. 胃肠病学, 2022, 27(5): 289-304.

[3]

HONG T C, EL-OMAR E M, KUO Y T, et al. Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2024, 9(1): 56-67.

[4]

LIU L G, NAHATA M C. Newer therapies for refractory helicobacter pylori infection in adults: a systematic review[J]. Antibiotics, 2024, 13(10): 965.

[5]

张阳阳, 齐子熠, 陈菁菁, 等. 全国172773例幽门螺杆菌感染患者中医证候分布的文献研究[J]. 中国中西医结合消化杂志, 2024, 32(4): 315-320, 334.

[6]

黄林, 杨洪伟, 邓树忠, 等. 香连片治疗脾胃湿热型慢性非萎缩性胃炎的临床疗效及作用机制研究[J]. 现代生物医学进展, 2020, 20(5): 988-991.

[7]

LIU M Q, HU Z Z, WANG C K, et al. The TLR/MyD88 signalling cascade in inflammation and gastric cancer: the immune regulatory network of Helicobacter pylori[J]. J Mol Med, 2023, 101(7): 767-781.

[8]

PACHATHUNDIKANDI S K, TEGTMEYER N, BACKERT S. Masking of typical TLR4 and TLR5 ligands modulates inflammation and resolution by Helicobacter pylori[J]. Trends Microbiol, 2023, 31(9): 903-915.

[9]

TEGTMEYER N, NEDDERMANN M, LIND J, et al. Toll-like receptor 5 activation by the CagY repeat domains of helicobacter pylori[J]. Cell Rep, 2020, 32(11): 108159.

[10]

MARTINELLI G, FUMAGALLI M, PIAZZA S, et al. Investigating the molecular mechanisms underlying early response to inflammation and helicobacter pylori infection in human gastric epithelial cells[J]. Int J Mol Sci, 2023, 24(20): 15147.

[11]

纪凌云, 吴俏兰, 陈泽涛, 等. 黄芩-黄连通过抑制TLR4/MyD88/NF-κB信号通路稳定动脉粥样硬化的易损斑块[J]. 中国实验方剂学杂志, 2024, 30(13): 28-36.

[12]

宋洁, 郭瑞芳, 聂虹, 等. 木香烃内酯对溃疡性结肠炎小鼠肠道免疫炎症的影响及其机制[J]. 广西医科大学学报, 2021, 38(12): 2300-2305.

[13]

王嫣, 杨卫平, 彭芳, 等. 吴茱萸碱通过TLR4/NF-κB通路抑制脂多糖诱导的人脐静脉内皮细胞损伤[J]. 细胞与分子免疫学杂志, 2019, 35(12): 1088-1093.

[14]

彭明蔚, 赵华鑫, 舒福, 等. 基于网络药理学和肠道菌群探讨香连丸改善高脂饮食诱导肥胖小鼠脂代谢紊乱的机制[J]. 中国中药杂志, 2023, 48(23): 6442-6456.

[15]

卢必超, 刘雪峰, 毛宁峰, 等. 连朴饮对Hp相关性胃炎大鼠胃黏膜炎性小体及炎症因子的影响[J]. 时珍国医国药, 2023, 34(4): 814-817.

[16]

李威莹, 吴威, 孟岩, 等. 湿热证动物模型造模方法及评价研究[J]. 世界科学技术-中医药现代化, 2021, 23(12): 4441-4451.

[17]

王郁金, 伽雨龙, 姜华, 等. 基于TGR5/GLP-1信号通路和肠道菌群探讨黄连温胆汤对湿热型糖尿病肠病大鼠的作用机制[J]. 中国实验方剂学杂志, 2025, 31(15): 10-18.

[18]

中华医学会消化病学分会幽门螺杆菌学组. 2022中国幽门螺杆菌感染治疗指南[J]. 中华消化杂志, 2022, 42(11): 745-756.

[19]

王萍, 卞立群, 杨倩, 等. 慢性胃炎中医诊疗专家共识(2023)[J]. 中华中医药杂志, 2023, 38(12): 5904-5911.

[20]

张伟, 康梦娇, 苟筱雯, 等. 重构本草——黄连[J]. 吉林中医药, 2024, 44(4): 467-470.

[21]

陈小宇, 李俊甫, 李颖硕, 等. 白木香茎皮的化学成分及其抗幽门螺旋杆菌活性研究[J]. 中国中药杂志, 2024, 49(15): 4100-4110.

[22]

谭朝丹, 楼冰, 顾伟鹰, 等. 不同比例黄连-吴茱萸配方颗粒/单/合煎对比分析[J]. 中国医院药学杂志, 2020, 40(21): 2238-2242, 2250.

[23]

杨乐, 徐梦婷, 蔡琳玲, 等. UHPLC-TOF-MS结合网络药理学与实验验证探讨香连丸治疗溃疡性结肠炎的作用机制[J]. 中国药学杂志, 2023, 58(12): 1084-1092.

[24]

韩莹, 蔡庆宇, 张岩. 香连丸对急性溃疡性结肠炎小鼠氧化应激介导的细胞自噬的影响研究[J]. 中国中医急症, 2019, 28(5): 851-853, 862.

[25]

苏景阳, 傅越, 王梦蕾, 等. 加味香连丸对急性放射性肠炎大鼠NF-κB信号通路的影响[J]. 中国中医急症, 2022, 31(7): 1153-1156.

[26]

WANG X P, ZHAO G, SHAO S H, et al. Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment[J]. Biochim Biophys Acta BBA Rev Cancer, 2024, 1879(5): 189139.

[27]

YANG X T, NIU P Q, LI X F, et al. Differential cytokine expression in gastric tissues highlights helicobacter pylori's role in gastritis[J]. Sci Rep, 2024, 14(1): 7683.

[28]

王杰, 高云霄, 马虹宇, 等. 基于网络药理学和实验验证探讨香连化浊方对慢性萎缩性胃炎的作用机制[J]. 中国实验方剂学杂志, 2022, 28(18): 161-168.

[29]

张前勇, 赵采芹, 石海英, 等. 鸡TIFA和TRAF6蛋白的分子特征及其基因在免疫器官中的表达特性[J]. 西南农业学报, 2023, 36(12): 2802-2813.

[30]

李慧敏, 高锦明. NF-κB在幽门螺杆菌诱导胃癌发展及治疗中的作用研究进展[J]. 现代肿瘤医学, 2023, 31(23): 4476-4480.

[31]

张雅迪, 杜方兵, 唐思慧, 等. TLRs/NF-κB信号通路及T淋巴细胞与重症肺炎患者预后的关系[J]. 国际呼吸杂志, 2023, 43(1): 75-80.

[32]

DINCǍ A L, MELIŢ L E, MǍRGINEAN C O. Old and new aspects of H. pylori-associated inflammation and gastric cancer[J]. Children, 2022, 9(7): 1083.

[33]

苏聃, 张莉, 潘冬宁. HP根除治疗对儿童肠道菌群结构的影响[J]. 湖南师范大学学报(医学版), 2024, 21(2): 73-77, 92.

[34]

王义江, 李祥. 幽门螺杆菌阳性十二指肠溃疡患儿幽门螺杆菌根除前后肠道菌群变化特征及临床意义[J]. 中华实用儿科临床杂志, 2022, 37(12): 939-943.

[35]

LIN J, ZHANG R Y, LIU H E, et al. Multi-omics analysis of the biological mechanism of the pathogenesis of non-alcoholic fatty liver disease[J]. Front Microbiol, 2024, 15: 1379064.

[36]

CHANG C S, LIAO Y C, HUANG C T, et al. Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice[J]. Cell Rep, 2021, 37(8): 110016.

[37]

LIU X M, MAO B Y, GU J Y, et al. Blautia-a new functional genus with potential probiotic properties[J]. Gut Microbes, 2021, 13(1): 1875796.

[38]

WU Y, YANG Y J, WANG L, et al. Effect of Bifidobacterium on osteoclasts: TNF-α/NF-κB inflammatory signal pathway-mediated mechanism[J]. Front Endocrinol, 2023, 14: 1109296.

[39]

胡莹莹, 林雪娟, 李星慧, 等. 幽门螺杆菌感染对慢性胃炎中医证素与肠道菌群的影响[J]. 中国中医药信息杂志, 2023, 30(8): 147-154.

2026年第44卷第7期

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doi: 10.13193/j.issn.1673-7717.2026.07.023

首发时间：2026-10-20
出版时间：2026-07-10

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基金

国家自然科学基金面上项目(82374205)

湖北省科学技术厅自然科学基金创新发展联合基金项目(2022CFD116)

湖北省时珍人才工程科研项目(鄂卫函〔2024〕256号)

武汉市中医药科研项目(WZ24A35)

作者信息

^1.湖北中医药大学中医学院，湖北　武汉　430065

^2.武汉市中西医结合医院，湖北　武汉　430033

^3.湖北时珍实验室，湖北　武汉　430060

^4.湖北中医药大学附属医院（湖北省中医院），湖北　武汉　430073

^5.湖北中医药大学实验动物中心，湖北　武汉　430065

^6.襄阳市中医医院（襄阳市中医药研究所），湖北　襄阳　441000

^7.湖北中医药大学第一临床学院，湖北　武汉　430061

通讯作者:

张霖（1981-），男，湖北潜江人，副主任医师，硕士研究生导师，博士，研究方向：中西医结合治疗消化疾病。E-mail：zhanglin_011@163.com。

胡运莲（1964-），女，湖北宜昌人，主任医师，博士研究生导师，博士，研究方向：中西医结合治疗消化疾病。E-mail：843214365@qq.com。

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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2026.07.023

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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