Hong Xinxin, Li Haiwen, Lin Yandan, Luo Liuru, Xu Weijun, Kang Jianyuan, Li Jingwei, Huang Bin, Xu Yifei, Pan Huafeng, Guo Shaoju
Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117062. doi: 10.1016/j.jep.2023.117062. Epub 2023 Aug 19.
Spasmolytic polypeptide-expressing metaplasia (SPEM) is characterized by mucus cell morphologies at the base of gastric glands, which is considered advanced SPEM when accompanied with an increase in transcripts associated with intestinal-type gastric cancer. Weiwei decoction (WWD) was modified from "Si-Jun-Zi Tang," which has been used for thousands of years in China against gastric atrophy and metaplasia.
To investigate the effects and potential mechanisms of WWD against advanced SPEM.
Liquid chromatography-mass spectrometry was employed to analyze the constituents of WWD. Five-month-infected Helicobacter pylori (H. pylori) Sydney strain 1 C57BL/6J mice and 6-week-old ATPase H/K transporting subunit alpha-knockout mice (Atp4a) were given folic acid (1.95 mg/kg) or WWD (13.65 g/kg, 27.30 g/kg, 54.60 g/kg) by gavage for one month.
WWD demonstrated beneficial effects on gastric mucosal pathology and mucus secretion. In H. pylori-infected mice, WWD effectively reduced the expression of GSII and inhibited the mRNA levels of key markers associated with advanced SPEM, including Clu, Cftr, Wfdc2, Dmbt1, and Gpx2. Similarly, in Atp4a mice, WWD significantly decreased the expressions of GSII and Clusterin, and inhibited the mRNA levels of Wfdc2, Cftr, Dmbt1, and Gpx2. Notably, WWD restored the expression of markers for chief cells (PGC, GIF) and parietal cells (ATP4A), particularly in the medium- and high-dose groups, indicating its potential anti-atrophy effect on H. pylori-infected and Atp4a mice. WWD administration resulted in a decline in TFF2 expression to baseline levels, suggesting that the mucous protection mediated by TFF2 was unaffected. Furthermore, the infiltration of CD163F4/80 M2 macrophages in the gastric mucosa of H. pylori-infected mice was reduced after WWD treatment, indicating a potential modulatory role of WWD on M2 macrophages.
WWD exerted protective effects against SPEM in H. pylori-infected and Atp4a mice. The optimal doses of WWD were found to be medium doses in H. pylori-infected mice and high doses in Atp4a mice. These effects include inhibition of transcripts associated with intestinal-type gastric adenocarcinoma, restoration of ATP4A and PGC expression, and reduction of M2 macrophage infiltration. These findings provide valuable insights into the therapeutic effects of WWD on advanced SPEM and highlight its potential as a treatment option.
表达解痉多肽的化生（SPEM）的特征是胃腺底部出现黏液细胞形态，当伴有与肠型胃癌相关转录本增加时，被认为是进展期SPEM。萎胃汤（WWD）由“四君子汤”化裁而来，在中国已应用数千年，用于治疗胃萎缩和化生。
探讨萎胃汤对进展期SPEM的作用及潜在机制。
采用液相色谱 - 质谱联用技术分析萎胃汤的成分。给感染幽门螺杆菌（H. pylori）五个月的悉尼株1 C57BL / 6J小鼠和6周龄的ATP酶H / K转运亚基α基因敲除小鼠（Atp4a）灌胃叶酸（1.95 mg / kg）或萎胃汤（13.65 g / kg、27.30 g / kg、54.60 g / kg），持续一个月。
萎胃汤对胃黏膜病理和黏液分泌具有有益作用。在感染H. pylori的小鼠中，萎胃汤有效降低了GSII的表达，并抑制了与进展期SPEM相关的关键标志物的mRNA水平，包括Clu、Cftr、Wfdc2、Dmbt1和Gpx2。同样，在Atp4a小鼠中，萎胃汤显著降低了GSII和Clusterin的表达，并抑制了Wfdc2、Cftr、Dmbt1和Gpx2的mRNA水平。值得注意的是，萎胃汤恢复了主细胞（PGC、GIF）和壁细胞（ATP4A）标志物的表达，特别是在中、高剂量组，表明其对感染H. pylori的小鼠和Atp4a小鼠具有潜在的抗萎缩作用。给予萎胃汤导致TFF2表达下降至基线水平，表明由TFF2介导的黏液保护作用未受影响。此外，萎胃汤治疗后，感染H. pylori小鼠胃黏膜中CD163F4 / 80 M2巨噬细胞的浸润减少，表明萎胃汤对M2巨噬细胞具有潜在的调节作用。
萎胃汤对感染H. pylori的小鼠和Atp4a小鼠的SPEM具有保护作用。发现萎胃汤在感染H. pylori的小鼠中的最佳剂量为中剂量，在Atp4a小鼠中为高剂量。这些作用包括抑制与肠型胃腺癌相关的转录本、恢复ATP4A和PGC表达以及减少M2巨噬细胞浸润。这些发现为萎胃汤对进展期SPEM的治疗作用提供了有价值的见解，并突出了其作为治疗选择的潜力。
