基于下丘脑代谢组学的麻杏石甘汤解热抗炎活性研究

Antipyretic and Anti-Inflammatory Activities of Maxing Shigan Decoction Based on Hypothalamic Metabolomics

    摘要
  • 摘要:
    目的 探讨麻杏石甘汤的解热抗炎作用及其对下丘脑代谢的影响。
    方法 采用腹腔注射脂多糖（LPS）建立大鼠发热模型，实验设正常组、模型组、对乙酰氨基酚组、麻杏石甘汤组。记录造模后 6 h内大鼠肛温的变化，以评价麻杏石甘汤解热作用；采用实时荧光定量逆转录聚合酶链反应（RT-qPCR）技术检测与炎症反应及体温调节相关的致热因子mRNA表达水平；使用酶联免疫吸附法（ELISA）测定前列腺素E2（PGE2）含量；通过邻甲酚酞络合酮（OCPC）比色法检测钙离子（Ca2+）含量；并通过非靶向下丘脑代谢组学及脂质组学富集代谢通路，研究麻杏石甘汤调控下丘脑代谢发挥解热作用的机制。
    结果 麻杏石甘汤可显著降低大鼠肛温（P0.001），回调下丘脑中致热因子 mRNA 水平（P0.05，P0.01，P0.001），减少脑脊液中 PGE2含量和Ca2+含量（P0.001），同时降低棕色脂肪中 PGC-1α 的 mRNA 表达（P0.01）。代谢组学分析结果表明，麻杏石甘汤可回调23种潜在差异小分子代谢物，主要涉及多胺生物合成途径。脂质组学研究结果显示，麻杏石甘汤能影响下丘脑中溶血磷脂酰胆碱（LPC）、脂肪酸（FA）、磷脂酰丝氨酸（PS）、磷脂酰甘油（PG）、鞘磷脂（SM）、己糖基神经酰胺（HexCer）等脂质水平，进而发挥解热作用。
    结论 麻杏石甘汤通过调节中枢神经系统内甘油磷脂代谢以及鞘胺醇代谢，影响中枢多胺生物合成，从而抑制内源性致热源释放，抑制过度产热反应以发挥解热作用。

     

    Abstract:
    OBJECTIVE To investigate the antipyretic and anti-inflammatory effects of Maxing Shigan Decoction and its influence on hypothalamic metabolism.
    METHODS Intraperitoneal injection of LPS was used to establish a rat fever model, and the rats were divided into control group, model group, acetaminophen group, and Maxing Shigan Decoction group. Rectal temperatures were recorded within 6 hours post-modeling to evaluate the antipyretic effect of Maxing Shigan Decoction. RT-qPCR was used to detect mRNA expression levels of pyrogenic factors associated with inflammatory responses and thermoregulation. The expression level of Prostaglandin E2 (PGE2) protein was measured using enzyme-linked immunosorbent assay (ELISA). Calcium ion (Ca2+) content was detected using the o-cresolphthalein complexone (OCPC) colorimetric method. Through non-targeted hypothalamic metabolomics and lipidomics, enriched metabolic pathways revealed the mechanism of action of Maxing Shigan Decoction in reducing fever and inflammation.
    RESULTS Maxing Shigan Decoction significantly reduced rectal temperature in rats (P0.001), downregulated the mRNA levels of inflammatory factors in the hypothalamus (P0.05), reduced the content of PGE₂ and the content of Ca2+ (P0.001) in cerebrospinal fluid, and simultaneously decreased the mRNA expression of PGC-1α in brown adipose tissue (P0.001). Metabolomics analysis revealed that the Maxing Shigan Decoction could regulate 23 potential differentially expressed metabolites, primarily involving the polyamine biosynthesis pathway. Lipidomics results showed that Maxing Shigan Decoction could affect the levels of lysophosphatidylcholine (LPC), fatty acids (FA), phosphatidylserine (PS), phosphatidylglycerol (PG), sphingomyelin (SM), and hexosylceramide (HexCer) in hypothalamus.
    CONCLUSION Maxing Shigan Decoction exerts its antipyretic effect by regulating glycerophospholipid and sphingosine metabolism in the central nervous system, thereby influencing central polyamine biosynthesis, inhibiting the release of endogenous pyrogens, and suppressing excessive thermogenesis.

     

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