Wang Jianghong, Wang Xiaoyuan, Song Yanru, Huang Zilin, Wu Han, Chang Liang, Huo Bingjie, Fan Guanwei
Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China.
The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Comb Chem High Throughput Screen. 2024 Sep 16. doi: 10.2174/0113862073325718240827073225.
The Precancerous Lesion of Gastric Cancer (PLGC) is an early stage in the development of gastric cancer. The clinical application of HPXLD has been found to be effective in treating PLGC, but the mechanism of how HPXLD acts on PLGC is still unclear.
The objectives of this study were to reveal the molecular mechanism of how HPXLD can be used to treat PLGC and investigate this mechanism through bioinformatics and experimental validation.
PLGC-associated target genes were identified through bioinformatics analysis. A rat model of PLGC was induced using N-methyl-N'-nitro-N-nitrosoquanidine (MNNG) in combination with ranitidine, hot saline, ethanol, and intermittent fasting, with interventions by HPXLD. The pathological alterations in gastric mucosa were assessed through Hematoxylin-eosin staining (HE). Immunohistochemistry (IHC) and Western blot analyses were employed to evaluate the changes in expression levels of inflammation-related proteins.
After conducting bioinformatics analysis, it was found that there were 23 HPXLDPLGC crossover genes, which were significantly enriched in the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. The results of HE showed that HPXLD was effective in improving gastric mucosal histopathological changes. Additionally, the IHC results demonstrated that HPXLD was able to downregulate the expression of IL-6, COX-2, MCP- 1, and MMP-9. Furthermore, Western blot analysis revealed that HPXLD was able to downregulate the expressions of IL-6, IL-17RA, ACT1, NF-κB, and TNF-α.
HPXLD has been shown to improve PLGC by reducing the expression of inflammation- related proteins. This suggests that HPXLD may potentially be a treatment option for PLGC.
胃癌前病变（PLGC）是胃癌发展的早期阶段。已发现化癖消痞灵（HPXLD）的临床应用对治疗PLGC有效，但HPXLD作用于PLGC的机制仍不清楚。
本研究的目的是揭示HPXLD用于治疗PLGC的分子机制，并通过生物信息学和实验验证来研究该机制。
通过生物信息学分析鉴定PLGC相关的靶基因。使用N-甲基-N'-硝基-N-亚硝基胍（MNNG）联合雷尼替丁、热盐水、乙醇和间歇性禁食诱导PLGC大鼠模型，并给予HPXLD干预。通过苏木精-伊红染色（HE）评估胃黏膜的病理改变。采用免疫组织化学（IHC）和蛋白质印迹分析来评估炎症相关蛋白表达水平的变化。
进行生物信息学分析后，发现有23个HPXLD-PLGC交叉基因，它们在IL-17信号通路、TNF信号通路和NF-κB信号通路中显著富集。HE结果显示，HPXLD能有效改善胃黏膜组织病理学变化。此外，IHC结果表明，HPXLD能够下调IL-6、COX-2、MCP-1和MMP-9的表达。此外，蛋白质印迹分析显示，HPXLD能够下调IL-6、IL-17RA、ACT1、NF-κB和TNF-α的表达。
已证明HPXLD通过降低炎症相关蛋白的表达来改善PLGC。这表明HPXLD可能是PLGC的一种治疗选择。
