Zhou Peng, Zheng Zi-Han, Wan Tao, Liao Chuan-Wen, Wu Jie
Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China.
World J Gastrointest Oncol. 2024 Jul 15;16(7):3158-3168. doi: 10.4251/wjgo.v16.i7.3158.
Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy.
To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG.
A CAG rat model was established by bacteria solution combined with N-methyl-N'-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay.
YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling.
Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.
慢性萎缩性胃炎（CAG）是一种常见的慢性胃炎，通常伴有肠化生和发育异常等癌前病变。中药在CAG治疗中的应用日益增多，显示出低副作用和显著疗效的良好前景。
探讨益气解毒化瘀汤（YJHD）对CAG癌前病变的药理作用。
采用细菌溶液联合N-甲基-N'-硝基-N-亚硝基胍建立CAG大鼠模型。通过苏木精-伊红、阿尔辛蓝和过碘酸-希夫染色进行组织病理学测量。采用酶联免疫吸附测定法检测血清炎症因子和胃黏膜相关因子水平。分别通过蛋白质印迹法和定量实时聚合酶链反应分析对蛋白质和mRNA水平进行定量。通过染色质免疫沉淀（ChIP）试验验证分子相互作用。
YJHD大大减轻了CAG大鼠胃黏膜的病理变化和癌前病变。同时，YJHD治疗降低了CAG大鼠血清炎症因子[白细胞介素（IL）-6、肿瘤坏死因子-α和C反应蛋白]水平，并提高了血清胃黏膜相关因子（胃泌素、胃蛋白酶、生长抑素和前列腺素E2）水平。此外，YJHD给药抑制了NLRP3炎性小体介导的细胞焦亡，以及TLR4/NF-κB和IL-6/STAT3信号通路的激活。机制上，ChIP实验证实NLRP3转录受TLR4/NF-κB和IL-6/STAT3信号调节。
综上所述，YJHD可能通过使TLR4/NF-κB和IL-6/STAT3通路失活，减轻CAG中NLRP3炎性小体的形成和上皮细胞焦亡。
