哮喘小鼠使用健脾补肺化痰方后不同时间短链脂肪酸及组胺的变化及潜在机制

The changes and potential mechanism of short-chain fatty acids and histamine in asthmatic mice at different time after using Jianpi Bufei Huatan Decoction

关键词:  哮喘  短链脂肪酸  组胺  时间变化  潜在靶点

Key words:  asthma  SCFAs  histamine  time change  potential target

摘要:

[目的] 观察健脾补肺化痰方对哮喘模型小鼠4周内的短链脂肪酸（SCFAs）及组胺（Histamine）的变化及潜在机制。[方法] 将16只BALB/c雌性小鼠分为MOD组和TCM组，用OVA致敏并激发复制哮喘大鼠模型，使用ELISA测定检测用药1~4周后粪便中的组胺水平，使用GC-MS分析检测用药1-4周后粪便中的SCFAs水平，运用网络药理学分析差异指标的潜在靶点及GO功能和KEGG通路富集分析，并通过分子对接技术验证靶点的可能性。[结果] 健脾补肺化痰方可以降低哮喘模型小鼠的组胺水平，尤其在用药第1、2周后明显（P<0.05）；且使用健脾补肺化痰方1周后，粪便中SCFAs除丁酸外，其他水平均有不同程度的升高（P<0.05），且戊酸、异戊酸、异丁酸、丙酸增长比更高；通过网络药理学分析及分子对接得出健脾补肺化痰方可能通过差异SCFAs及组胺治疗哮喘的靶点及其通路。[结论] 健脾补肺化痰方用药1周后，哮喘模型小鼠的组胺下降及戊酸、异戊酸、异丁酸增长明显，且健脾补肺化痰方在哮喘早期可能通过乙酸、戊酸、丙酸、组胺等作用于AGTR1、CXCR4等靶点发挥减轻气道炎症及气道高反应的作用。

Abstract:

[Objective] To observe the effect and potential mechanism of Jianpi Bufei Huatan Decoction on the changes of short chain fatty acids(SCFAs) and histamine in asthma model mice within 4 weeks.[Methods] Sixteen BALB/c female mice were divided into MOD group and traditional Chinese medicine(TCM) group. The asthma rat model was sensitized and challenged with OVA. The histamine level in feces was measured by ELISA after 1-4 weeks of treatment. GC-MS analysis was used to detect the level of SCFAs in feces after 1-4 weeks of treatment. Network pharmacology analysis was employed to identify potential targets of differential indicators,followed by GO functional and KEGG pathway enrichment analysis. Molecular docking techniques were then used to validate the feasibility of these targets..[Results] Jianpi Bufei Huatan Decoction can reduce the histamine level of asthma model mice,especially after the first and second weeks of medication(P<0.05);after one week of using Jianpi Bufei Huatan Decoction,except for butyric acid,other levels of short-chain fatty acids in feces increased to varying degrees(P<0.05),and the growth ratios of valeric acid,isovaleric acid,isobutyric acid and propionic acid were higher. Through network pharmacology analysis and molecular docking, it has been suggested that the Jianpi Bupul Huatan Decoction may target asthma by regulating differential SCFAs and histamine, thereby influencing related pathways..[Conclusion] After one week of treatment with Jianpi Bufei Huatan Decoction,histamine decreased and valeric acid,isovaleric acid and isobutyric acid increased significantly in asthmatic model mice. In the early stage of asthma,Jianpi Bufei Huatan Decoction may reduce airway inflammation and airway hyperresponsiveness by acting on AGTR1,CXCR4 and other targets through acetic acid,valeric acid,propionic acid and histamine.