School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, 310053, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, 310053, China.
J Ethnopharmacol. 2023 Jun 12;309:116345. doi: 10.1016/j.jep.2023.116345. Epub 2023 Mar 9.
Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled.
The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism.
The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin, pepsinogen, and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6, IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy, respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining.
WEN could dose-dependently lower the serum level of IL-1β and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2, and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG.
This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways' activation.
胃尔宁片（WEN）是一种传统的中药，多年来广泛应用于临床治疗慢性萎缩性胃炎（CAG）。然而，WEN 对 CAG 的潜在机制仍未被揭示。
本研究旨在阐明 WEN 对 CAG 的治疗作用，并阐明其潜在机制。
采用灌胃大鼠的方法建立 CAG 模型，用建模溶液（由 2%水杨酸钠和 30%酒精组成）和不规则饮食以及自由接触 0.1%氨溶液两个月。酶联免疫吸附试验用于测量血清胃泌素、胃蛋白酶原和炎症细胞因子的水平。qRT-PCR 用于测量胃组织中 IL-6、IL-18、IL-10、TNF-α 和 γ-IFN 的 mRNA 表达。通过苏木精和伊红染色和透射电子显微镜分别观察胃黏膜的病理变化和超微结构。AB-PAS 染色用于观察胃黏膜的肠上皮化生。免疫组化和 Western blot 用于测量胃组织中线粒体凋亡相关蛋白和 Hedgehog 通路相关蛋白的表达水平。免疫荧光染色用于测定 Cdx2 和 Muc2 蛋白的表达。
WEN 可剂量依赖性地降低血清中 IL-1β 的水平和胃组织中 IL-6、IL-8、IL-10、TNF-α 和 γ-IFN 的 mRNA 表达。此外，WEN 还能显著减轻胃黏膜下层胶原沉积，调节 Bax、Cleaved-caspase9、Bcl2 和 Cytochrome c 的表达，减少胃黏膜上皮细胞凋亡，并维持胃黏膜屏障的完整性。此外，WEN 可降低 Cdx2、Muc2、Shh、Gli1 和 Smo 的蛋白表达，逆转胃黏膜的肠上皮化生，从而阻止 CAG 的进展。
本研究表明 WEN 对改善 CAG 和逆转肠上皮化生有积极作用。这些功能与抑制胃黏膜细胞凋亡和抑制 Hedgehog 通路的激活有关。
