抽搐解痉多肽表达的不典型化生（SPEM）的特点是胃腺底部黏液细胞形态学的改变，当与肠式胃癌相关的转录本增加时，被视为SPEM的进展。"卫卫"水煎剂（WWD）是由"四君子汤"改制而来，这种汤在中国有数千年的历史，被用于治疗胃萎缩和异型化生。为了研究WWD对进展性SPEM的作用和潜在机制，采用液相色谱质谱分析了WWD的成分。给予五个月感染了幽门螺杆菌（H. pylori）Sydney菌株1的C57BL/6J小鼠和6周大的ATP酶H+/K+转运亚基α敲除小鼠（Atp4a-/-）富尔酸（1.95 mg/kg）或WWD（13.65 g/kg、27.30 g/kg、54.60 g/kg）灌胃一个月。 结果显示，WWD对胃粘膜病理和黏液分泌具有有益作用。在感染H. pylori的小鼠中，WWD有效降低了GSII的表达，并抑制了与进展性SPEM相关的关键标志物Clu、Cftr、Wfdc2、Dmbt1和Gpx2的mRNA水平。类似地，在Atp4a-/-小鼠中，WWD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，WWD在中、高剂量组中恢复了胃主细胞标记物（PGC、GIF）和壁细胞标记物（ATP4A）的表达，表明其对H. pylori感染和Atp4a-/-小鼠的潜在防萎缩作用。WWD治疗导致TFF2表达降至基线水平，说明TFF2介导的黏液保护未受影响。此外，H. pylori感染小鼠胃粘膜CD163+F4/80+ M2巨噬细胞浸润在WWD治疗后减少，表明WWD可能对M2巨噬细胞发挥调节作用。 在H. pylori感染和Atp4a-/-小鼠中，WWD对SPEM具有保护作用。在H. pylori感染小鼠中，中剂量组在Atp4a-/-小鼠中为高剂量组，这些作用包括抑制与肠式胃腺癌相关的转录本、恢复ATP4A和PGC的表达以及减少M2巨噬细胞浸润。这些发现为WWD治疗进展性SPEM的疗效提供了有价值的见解，并突显了其作为一种治疗选择的潜力。版权所有 © 2023。由Elsevier B.V.出版。

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 CD163+F4/80+ 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.Copyright © 2023. Published by Elsevier B.V.