[1]马宝柱,陈国明,周云波,等.温中益气方调控TLR4-NF-κΒ通路对胃溃疡的抗炎机制研究[J].陕西中医,2026,(1):28-33,39.[doi:DOI:10.3969/j.issn.1000-7369.2026.01.005]
　MA Baozhu,CHEN Guoming,ZHOU Yunbo,et al.Study on the anti-inflammatory mechanism of Wenzhong Yiqi decoction on gastric ulcer by regulating TLR4-NF-κB pathway[J].,2026,(1):28-33,39.[doi:DOI:10.3969/j.issn.1000-7369.2026.01.005]
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温中益气方调控TLR4-NF-κΒ通路对胃溃疡的抗炎机制研究

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2026年1期
页码:
28-33,39
栏目:
基础研究
出版日期:
2026-01-05

文章信息/Info

Title:
Study on the anti-inflammatory mechanism of Wenzhong Yiqi decoction on gastric ulcer by regulating TLR4-NF-κB pathway
作者:
马宝柱; 陈国明; 周云波; 韩丽; 周国兴
（黑龙江中医药大学附属第一医院，黑龙江 哈尔滨 150040)
Author(s):
MA Baozhu; CHEN Guoming; ZHOU Yunbo; HAN Li; ZHOU Guoxing
（The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China）
关键词:
胃溃疡; 温中益气方; 氧化应激; 炎症; 肿瘤坏死因子; 胃黏膜
Keywords:
Gastric ulcer; Wenzhong Yiqi decoction; Oxidative stress; Tumor necrosis factor; Gastric mucosa
分类号:
R 573
DOI:
DOI:10.3969/j.issn.1000-7369.2026.01.005
文献标志码:
A
摘要:
目的：通过乙酸灼烧法建立大鼠胃溃疡模型，探讨温中益气方对胃溃疡模型大鼠的治疗效果和作用机制。方法：准备SD大鼠60只，随机分为假手术组、模型组、奥美拉唑组以及温中益气方低、中、高剂量组，每组各10只。除假手术组，其余各组均使用乙酸灼烧法来制备胃溃疡模型。各组大鼠每日给药灌胃给药1次，温中益气方低、中、高剂量组大鼠给药剂量分别为0.6、1.2、2.4 g/kg，奥美拉唑组大鼠给予0.36 g/kg的奥美拉唑肠溶胶囊内容物，假手术组大鼠给予等体积0.9%氯化钠溶液灌胃。各组连续灌胃给药14 d。末次给药后取材检测相关指标，包括胃酸pH；血清中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-PX）、一氧化氮（NO）、诱导型一氧化氮合酶（i-NOS）和总一氧化氮合成酶（t-NOS）；测定大鼠溃疡面积和溃疡抑制率；苏木精-伊红染色法（HE）观察各组大鼠胃溃疡组织病理形态变化；酶联免疫法（ELISA）检测各组大鼠胃组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）蛋白含量；RT-qPCR检测溃疡组织中mRNA表达情况；Western blot检测相关蛋白表达情况。结果：与假手术组比较，模型组大鼠胃酸pH值有降低趋势；与模型组相比，温中益气方低剂量组胃酸pH值无明显变化，温中益气方中、高剂量组胃酸pH值显著升高（P<0.05）。与模型组相比，温中益气方各剂量组溃疡面积显著减小（P<0.05）。与假手术组比较，模型组大鼠血清中NO、SOD、GSH-PX水平显著降低（P<0.01），t-NOS、MDA水平显著升高（P<0.01）。与模型组比较，各给药组大鼠血清中NO、t-NOS、SOD、GSH-PX水平显著升高（P<0.05）；i-NOS、MDA水平显著降低（P<0.05）。病理观察显示，温中益气方高剂量组大鼠溃疡周围胃黏膜的形态结构已进一步趋于正常，损伤部位已见少许新生肉芽组织。与假手术组相比，模型组大鼠胃组织内TNF-α和IL-6蛋白含量明显增加（P<0.05）；各给药组大鼠胃组织中TNF-α和IL-6蛋白含量明显降低（P<0.05）。与假手术组相比，模型组大鼠胃溃疡组织中Toll样受体4（TLR4）、髓分化因子88（MyD88）、核因子κB（NF-κΒ） p65 mRNA表达水平有明显提升（P<0.05）；与模型组相比，各给药组大鼠胃溃疡组织中TLR4、MyD88、NF-κΒ p65 mRNA表达水平显著降低（P<0.05），各给药组大鼠胃溃疡组织中TLR4、MyD88、NF-κΒ p65蛋白表达水平显著降低（P<0.05）。结论：温中益气方对大鼠胃溃疡具有较强的治疗作用，能够促进溃疡的愈合，作用机制可能与TLR4-NF-κΒ信号通路有关，通过抑制氧化应激，抑制炎症刺激，促进胃黏膜再生修复并发挥作用。
Abstract:
Objective:To explore the therapeutic effect and mechanism of Wenzhong Yiqi decoction on gastric ulcer in rats by acetic acid burning method.Methods:Sixty SD rats were randomly divided into sham operation,model,omeprazole,and low-,medium-,and high-dose treatment groups,with 10 rats in each group.Except the sham operation group,the other groups were used acetic acid burning method to establish gastric ulcer model.The rats in each group were given intragastric administration of Wenzhong Yiqi decoction once a day.The low-,medium-,and high-dose group was given 0.6,1.2 and 2.4 g/kg.The rats in omeprazole positive group were given the contents of omeprazole enteric-coated capsules at a dose of 0.36 g/kg,and the rats in sham operation group were given the same volume of 0.9% sodium chloride solution by gavage.The rats in each group were treated by intragastric administration for 14 days.After the last administration,the relevant parameters were measured,including gastric acid pH;serum levels of superoxide dismutase (SOD),malondialdehyde (MDA),glutathione peroxidase (GSH-PX),nitric oxide (NO),inducible nitric oxide synthase (i-NOS) and total nitric oxide synthase (t-NOS) were measured.The ulcer area and ulcer inhibition rate were measured.Hematoxylin-eosin staining (HE) was used to observe the pathological changes of gastric ulcer tissue in each group.The protein levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in gastric tissue were detected by enzyme-linked immunosorbent assay (ELISA).RT-qPCR was used to detect the mRNA expression in ulcer tissue.Western blotting was used to detect the expression of related proteins.Results:Compared with the sham-operation group,the pH value of gastric acid in the model group tended to decrease.Compared with the model group,the pH value of gastric acid in the low dose of group did not change significantly,while the pH value of gastric acid in the medium and high dose groups increased significantly (P<0.05) and the ulcer area of Wenzhong Yiqi decoction treatment groups was significantly reduced (P<0.05).Compared with the sham operation group,the levels of NO,SOD and GSH-PX in the serum of the model group were significantly decreased (P<0.01),and the levels of t-NOS and MDA were significantly increased (P<0.01).Compared with the model group,the serum levels of NO,t-NOS,SOD and GSH-PX in each administration group were significantly increased (P<0.05).The levels of i-NOS and MDA were significantly decreased (P<0.05).Pathological observation showed that after the treatment with Wenzhong Yiqi decoction,the morphological structure of gastric mucosa around the ulcer in the high-dose group tended to be further normal,and a little new granulation tissue was observed in the injured site.Compared with the sham operation group,the TNF-α and IL-6 protein levels in the gastric tissue of the model group were significantly increased (P<0.05).The contents of TNF-α and IL-6 protein in gastric tissue of rats in each administration group were significantly decreased (P<0.05).Compared with the sham operation group,the expression levels of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB) p65 mRNA in the model group were significantly increased (P<0.05).Compared with the model group,the expression levels of TLR4,MyD88 and NF-κΒ p65 mRNA in the gastric ulcer tissue of the rats in each treatment group were significantly decreased (P<0.05),and the protein expression levels of TLR4,MyD88 and NF-κΒ p65 in the gastric ulcer tissues of the drug groups were significantly decreased (P<0.05).Conclusion:Wenzhong Yiqi decoction has a strong therapeutic effect on gastric ulcer in rats and can promote the healing of gastric ulcer possibly by inhibiting the TLR4-NF-κΒ signaling pathway and promoting the regeneration of gastric mucosa by inhibiting oxidative stress and inflammatory stimulation.

参考文献/References:

[1]李志勇,吴耀南.中医药治疗消化性溃疡研究进展[J].江西中医学院学报,2011,23(3):77-80.
[2]吴焕,肖慧琳,罗静,等.中药防治乙酸型胃溃疡研究进展[J].壮瑶药研究,2023,15(3):419-422.
[3]王影,任欢,李猛,等.健脾温中益气方联合针灸对结直肠癌术后患者胃肠道功能及胃肠道激素水平的影响[J].河北中医,2024,46(6):992-995.
[4]马宝柱,马晨曦,周国兴,等.基于网络药理学探讨温中益气方抗胃溃疡的作用机制[J].中医药信息,2021,38(1):12-16.
[5]徐斐翔,龚振宇,薛明明.半夏泻心汤对大鼠乙酸型胃溃疡的保护作用[J].中国临床医学,2020,27(6):978-982.
[6]姜圣钰.清胃止痛微丸对大鼠乙酸型胃溃疡的治疗作用及机制研究[D].长春：吉林大学,2023.
[7]祝红,张瑾,黄胜楠,等.基于中西医临床病证特点的胃溃疡动物模型研究进展[J].中国实验方剂学杂志,2022,28(1):234-240.
[8]韩广明,赵炜,吕迎春.温中和胃汤联合耳穴压豆对脾胃虚寒型慢性胃炎患者治疗疗效及对血清VIP、MTL水平的影响[J].辽宁中医杂志,2024,51(7):92-96.
[9]OKABE S,AMAGASE K.An overview of acetic acid ulcer models-the history and state of the art of peptic ulcer research[J].Biol Pharm Bull,2005,28(8):1321-1341.
[10]徐叔云.药理实验方法学[M].3版.北京:人民卫生出版社,2002:202-205.
[11]陈思清,周赛男,韩运宗,等.黄芪建中汤对胃溃疡大鼠血清炎症因子、胃黏膜表皮生长因子受体表达的影响[J].陕西中医,2023,44(8):1032-1036.
[12]张维,戈之铮,陆红.2013—2019年幽门螺杆菌阳性消化性溃疡变化特点[J].胃肠病学,2020,25(11):670-672.
[13]魏广义,刘楠楠,王淑美,等.抗胃溃疡中药实验研究进展[J].中药药理与临床,2020,36(5):228-232.
[14]张雷,符萌,张伟,等.海藻提取物对小鼠酒精性胃溃疡的保护作用[J].中国海洋药物,2021,40(2):28-34.
[15]傅文录.金寿老人药解注解[M].香港:繁荣出版社有限公司,2015:26.
[16]张金鑫.本经疏证[M].北京:学苑出版社,2009:15.
[17]GOORANI S,ZHALEH M,ZANGENEH A,et al.The aqueous extract of Glycyrrhiza glabra effectively prevents induced gastroduodenal ulcers:Experimental study on Wistar rats[J].Comp Clin Path,2019,28:339-347.
[18]KIM K J,KIM E,KANG W S,et al.SR-5,the specific ratio of Korean multi-herbal formula:An evaluation of antiulcerogenic effects on experimentally induced gastric ulcers in mice[J].Dose Response,2021,19(4):1044329.
[19]MAGIEROWSKI M,MAGIEROWSKA K,KWIECIEN S,et al.Gaseous mediators’ nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity,protection and ulcer healing[J].Molecules,2015,20(5):9099-9123.
[20]WALLACE J L.Nitric oxide in the gastrointestinal tract:Opportunities for drug development[J].Br J Pharmacol,2019,176(2):147-154.
[21]HOWDIESHELL T R,WEBB W L,SATHYANA R,et al.Inhibition of inducible nitric oxide synthase results in reductions in wound vascular endothelial growth factor expression,granulation tissue formation,and local perfusion[J].Surgery,2003,133(5):528-537.
[22]BOUTON C,DEMPLE B.Nitric oxide-inducible expression of heme oxygenase-l in human cells：Translation-independent stabilization of the mRNA and evidence for direct action of nitric oxide[J].J Biol Chem,2000,275(42):32688-32693.
[23]HOEKSTRA K A,GODIN D V,CHENG K M.Protective role of heme oxygenase in the blood vessel wall during atherogenesis[J].Biochem Cell Biol,2004,82(3):351-359.
[24]CHATTERJEE A,CHATTERJEE S,BISWAS A,et al.Gallic acid enriched fraction of Phyllanthus emblica potentiates indomethacin-induced gastric ulcer healing via e-NOS-dependent pathway[J].Evid Based Complement Alternat Med,2012,2012:487380.
[25]SHI H,HUANG X,YAN Z,et al.Effect of clostridium perfringens type C on TLR4/MyD88/NF-κB signaling pathway in piglet small intestines[J].Microb Pathog,2019,135(1):10356-10367.

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备注/Memo

备注/Memo:
黑龙江省中医药管理局立项研究课题（ZHY2022145）;黑龙江省中医药科研项目（ZHY19-027）
更新日期/Last Update: 2026-01-08