摘要
背景：黄芪皂苷IV（AS-IV）对各种因素引起的胃肠道损伤具有保护作用。目的：本研究旨在探讨 AS-IV 对慢性萎缩性胃炎（CAG）的影响，并阐明其分子机制：方法：采用反转录聚合酶链反应和Western印迹分析法分别评估蛋白酶激活受体-1（PAR-1）及相关蛋白的mRNA和蛋白水平。此外，用 N-甲基-N'-硝基-N-亚硝基胍（MNNG）处理 GES-1 细胞后，通过酶联免疫吸附法测定了炎症因子的水平。用 MNNG 诱导大鼠建立 CAG 模型，同时用 AS-IV 治疗 10 周。随后收集血清样本以评估反映炎症标志物的蛋白质表达水平。胃组织切片用于苏木精和伊红染色、免疫组化分析以及 p-NF-κB p65 和 PAR-1 信号传导的评估：体外实验表明，AS-IV 和 MNNG 处理后，PAR-1 的 mRNA 水平上调。相反，抑制 PAR-1 的表达会逆转 AS-IV 对 MNNG 处理的 GES-1 细胞的治疗效果，导致环氧化酶-2 和 p-NF-κB p65 的表达增加。此外，抑制 PAR-1 还能显著逆转 MNNG 诱导的炎症因子，包括 IL 的增加。体内实验验证进一步证实，AS-IV 治疗后 PAR-1 表达的上调对 CAG 大鼠的胃黏膜具有保护作用：总之，本研究结果表明，AS-IV对MNNG诱导的CAG具有治疗作用，其机制可能与凝血酶/PAR-1信号通路密切相关。本研究为进一步探讨 AS-IV 治疗人类 CAG 的药理作用提供了理论基础。Background: Astragaloside IV (AS-IV) has demonstrated a protective effect against gastrointestinal tract injury induced by various factors. However, its potential mechanism against chronic atrophic gastritis (CAG) remains unknown.
Purpose: The objective of the present study was to investigate the impact of AS-IV on CAG and elucidate its molecular mechanism.
Methods: The mRNA and protein levels of protease-activated receptor-1 (PAR-1) and related proteins were assessed using reverse transcription-polymerase chain reaction and western blot analyses, respectively. In addition, the levels of inflammatory factors were measured via enzyme-linked immunosorbent assay in GES-1 cells following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The CAG model was established in rats induced with MNNG and concurrently treated with AS-IV for 10 weeks. Subsequently, serum samples were collected to assess the expression levels of proteins reflecting inflammatory markers. The gastric tissue sections were used for hematoxylin and eosin staining, immunohistochemical analysis, and the assessment of p-NF-κB p65 and PAR-1 signaling.
Results: In-vitro experiments demonstrated that the mRNA levels of PAR-1 were upregulated following treatment with AS-IV and MNNG. Conversely, inhibition of PAR-1 expression reversed the therapeutic effects of AS-IV on MNNG-treated GES-1 cells, leading to increased expression of cyclooxygenase-2 and p-NF-κB p65. In addition, PAR-1 inhibition notably reversed MNNG-induced inflammatory factors, including IL increase. In-vivo experimental validation further confirmed that the upregulation of PAR-1 expression following treatment with AS-IV exerted a protective effect on the gastric mucosa of CAG rats.
Conclusion: In conclusion, the findings of the present study suggested that AS-IV exhibited therapeutic efficacy against CAG induced by MNNG; its mechanism may be closely associated with the thrombin/PAR-1 signaling pathway. The present study provides a theoretical foundation for further exploration of the pharmacological effects of AS-IV on the treatment of human CAG.
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