健脾消石片对脾气虚型功能性消化不良大鼠的蛋白质组学研究。

BACKGROUND: Jianweixiaoshi tablets (JWXS) is widely used in traditional Chinese medicine for treating functional dyspepsia with spleen deficiency (SD-FD) in China. However, the molecular mechanisms underlying the therapeutic effects of JWXS remain incompletely understood. METHODS: Functional dyspepsia was induced in rats with spleen deficiency by iodoacetamide in combination with the modified multiple platform method. The SD-FD rats were administered JWXS at both low and high doses, as well as domperidone. We conducted a comprehensive evaluation of the treatment effects of JWXS, including body weight, gastrointestinal motility, immune organ index, biochemical analysis, gastrointestinal hormones, and hematological studies. Quantitative proteomic analysis based on data-independent acquisition (DIA) was used to determine the changes in protein profiles of gastric and duodenal tissues in SD-FD rats and JWXS intervention rats. RESULTS: The results showed that JWXS effectively alleviated gastrointestinal motility disorders in SD-FD rats, as indicated by accelerated gastric emptying and intestinal propulsion, increased levels of gastrin, motilin, and ghrelin, and reduced levels of cholecystokinin-octapeptide, vasoactive intestinal peptide, and somatostatin. Additionally, JWXS increased the spleen and thymus index, increased %lymphocyte in blood, reduced white blood cell count and %neutrophil, and improved immune function. Through quantitative proteomic analysis of gastric tissues, we identified 333 differentially expressed proteins in the JWXS treatment group and the model group. Notably, the mechanism by which JWXS accelerated gastric emptying may be related to PLC-γ and SERCA2 in the calcium signaling pathway. Furthermore, JWXS treatment altered the expression of 732 proteins in rat duodenal samples. The differentially expressed proteins were enriched in immune-related functions and pathways, including antigen processing and presentation, as well as the intestinal immune network for IgA production. CONCLUSION: In conclusion, JWXS exhibits a multi-faceted impact on various pathways, demonstrating its efficacy in treating SD-FD. These findings provide a foundation for the clinical application of JWXS in managing SD-FD.

背景：健胃消食片（JWXS）在中国被广泛用于治疗脾虚型功能性消化不良（SD-FD）。然而，JWXS 的治疗效果的分子机制仍不完全清楚。

方法：采用碘乙酰胺联合改良多平台法诱导脾虚型功能性消化不良大鼠。SD-FD 大鼠分别给予 JWXS 低、高剂量和多潘立酮治疗。我们对 JWXS 的治疗效果进行了综合评价，包括体重、胃肠动力、免疫器官指数、生化分析、胃肠激素和血液学研究。基于数据非依赖性采集（DIA）的定量蛋白质组学分析用于确定 SD-FD 大鼠和 JWXS 干预大鼠胃和十二指肠组织的蛋白质图谱变化。

结果：结果表明，JWXS 有效缓解了 SD-FD 大鼠的胃肠动力障碍，表现为胃排空和肠推进加速，胃泌素、胃动素和 ghrelin 水平升高，胆囊收缩素-八肽、血管活性肠肽和生长抑素水平降低。此外，JWXS 增加了脾和胸腺指数，增加了血液中的淋巴细胞百分比，降低了白细胞计数和中性粒细胞百分比，改善了免疫功能。通过胃组织的定量蛋白质组学分析，我们在 JWXS 治疗组和模型组中鉴定出 333 个差异表达蛋白。值得注意的是，JWXS 加速胃排空的机制可能与钙信号通路中的 PLC-γ 和 SERCA2 有关。此外，JWXS 治疗改变了大鼠十二指肠样本中 732 种蛋白质的表达。差异表达蛋白富集在免疫相关功能和途径中，包括抗原加工和呈递以及 IgA 产生的肠道免疫网络。

结论：总之，JWXS 对多种途径产生多方面影响，证明其在治疗 SD-FD 方面的疗效。这些发现为 JWXS 在治疗 SD-FD 中的临床应用提供了基础。