Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, 730000, China; Gansu Province Laboratory Animal Industry Technology Center, Lanzhou, Gansu, 730000, China.
Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, 730000, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):116715. doi: 10.1016/j.jep.2023.116715. Epub 2023 Jun 10.
ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsha-Liujunzi-Tang (XSLJZT) is a classical formula for treating the diseases of digestive system, which can effectively and significantly improve the symptoms of functional dyspepsia (FD) patients. The main function of XSLJZT is to benefit Qi and spleen, and harmonize stomach. AIM OF THE STUDY: The purpose of this study was to investigate the intervention effect of XSLJZT on duodenal mucosal injury in FD rats and the response mechanism of MC/Tryptase/PAR-2 signal pathway. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively identify the chemical component of XSLJZT. A comprehensive modeling method (iodoacetamide infusion + irregular diet + swimming exhaustion) was used to construct the FD rat model. XSLJZT decoction was given to intervene FD rats for 2 weeks. The indicators of digestive function including body mass, 3-h food intake, visceral sensitivity, gastric emptying rate and intestinal propulsion rate were routinely measured for FD rats. The pathological changes of duodenum and microstructure of intestinal epithelial cells were observed by HE staining and transmission electron microscopy respectively. The inflammatory factors (VCAM-1, IL-6, TNF-α, and ICAM-1) and histamine content were evaluated by enzyme-linked immunosorbent assay (ELISA). The expression levels of Tryptase, PAR-2, ZO-1, β-catenin, p-NF-κBp65 and p-ERK1/2 in duodenal tissues were measured by Western blot (WB) and immunofluorescence colony-staining (IFC). RESULTS: XSLJZT administration significantly improved the survival of FD rats, increased body mass and 3-h food intake, improved visceral sensitivity, and restored gastric emptying rate and intestinal propulsion rate. HE staining showed that XSLJZT recovered the structure of duodenal mucosal and reduced inflammatory infiltration. ELISA revealed that XSLJZT reduced the content of inflammatory factors (VCAM-1, IL-6, TNF-α, and ICAM-1) and histamine. In addition, WB and IFC uncovered that the protein levels of ZO-1 and β-catenin were up-regulated and MC/Tryptase/PAR-2 signaling pathway was inhibited by XSLJZT. CONCLUSION: XSLJZT significantly improved the integrity of duodenal mucosa and decreased the inflammation in FD rats through the inhibition of MC/Tryptase/PAR-2 signaling pathway response.
民族药理学相关性：香砂六君子汤（XSLJZT）是一种治疗消化系统疾病的经典方剂，能有效显著改善功能性消化不良（FD）患者的症状。XSLJZT 的主要功能是益气健脾，调和胃气。
研究目的：本研究旨在探讨 XSLJZT 对 FD 大鼠十二指肠黏膜损伤的干预作用及 MC/Tryptase/PAR-2 信号通路的反应机制。
材料与方法：采用超高效液相色谱-串联质谱（UPLC-MS/MS）对 XSLJZT 的化学成分进行定性和定量分析。采用碘乙酰胺灌注+不规则饮食+游泳疲劳综合建模方法构建 FD 大鼠模型。给予 XSLJZT 煎剂干预 FD 大鼠 2 周。常规测量 FD 大鼠的体质量、3h 进食量、内脏敏感性、胃排空率和肠推进率等消化功能指标。HE 染色和透射电镜分别观察十二指肠的病理变化和肠上皮细胞的超微结构。酶联免疫吸附试验（ELISA）评价 VCAM-1、IL-6、TNF-α和 ICAM-1 等炎症因子和组胺含量。Western blot（WB）和免疫荧光集落染色（IFC）检测十二指肠组织中 Tryptase、PAR-2、ZO-1、β-catenin、p-NF-κBp65 和 p-ERK1/2 的表达水平。
结果：XSLJZT 给药可显著提高 FD 大鼠的存活率，增加体质量和 3h 进食量，改善内脏敏感性，恢复胃排空率和肠推进率。HE 染色显示 XSLJZT 恢复了十二指肠黏膜的结构，减少了炎症浸润。ELISA 显示 XSLJZT 降低了炎症因子（VCAM-1、IL-6、TNF-α和 ICAM-1）和组胺的含量。此外，WB 和 IFC 揭示 XSLJZT 通过抑制 MC/Tryptase/PAR-2 信号通路反应，上调 ZO-1 和 β-catenin 的蛋白水平。
结论：XSLJZT 通过抑制 MC/Tryptase/PAR-2 信号通路反应，显著改善 FD 大鼠十二指肠黏膜的完整性，减轻炎症反应。
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