比那甫西颗粒对干酵母致热大鼠模型的解热作用机制研究

Antipyretic mechanism of Binafuxi Granules on dry yeast-induced fever rat model

摘要

目的: 本研究评估比那甫西颗粒对干酵母诱导大鼠发热模型的解热效果,并深入探讨其解热作用机制,以期为比那甫西颗粒的临床应用提供理论依据。方法: 建立干酵母诱导大鼠发热模型,通过大鼠肛温测量、ELISA 检测、qPCR 检测和 Western blot 检测等方法考察比那甫西颗粒对真菌性发热大鼠解热的作用机制。结果: 千酵母诱导的发热模型实验结果显示,与模型组相比,比那甫西颗粒各给药组大鼠连续时间段内肛温均显著下降 (P<0.01) ;与模型组相比,比那甫西颗粒各给药组明显降低大鼠血清中致热炎性因子白细胞介素-1β (interleukin-1β,IL-1β) 、白细胞介素-6 (interleukin-6,IL-6) 、肿瘤坏死因子-α (tumor necrosis factor-α,TNF-α) 和干扰素-γ (inerferon-γ,IFN-γ) 的含量以及下丘脑组织中前列腺素 E2 (prostaglandin E2, PGE2) 和环磷酸腺苷 (cyclic adenosine monophosphat,cAMP) 的含量 (P<0.01),明显抑制大鼠下丘脑中 Toll样受体4 (Toll-like receptor4,TLR4) 、环氧合酶-2 (cyclooxygenase 2,COX2) 、核因子κp65 (nuclear factor-κB p65,NF— κB 65) 等免疫和炎症反应相关基因的 mRNA 表达水平 (P<0.05),显著下调模型大鼠下丘脑中免疫和炎症反应相关蛋白 TLR4、p-NF-κB p65的表达水平 (P<0.05) 。结论: 比那甫西颗粒可能通过调控TLR4/NF-κB 信号通路,抑制致热炎性因子的产生,发挥解热作用。

Abstract

Objective: To evaluate the antipyretic effect of Binafuxi Granules on dry yeast-induced fever model in rats and further explore its antipyretic mechanism, in order to provide a theoretical basis for the clinical application of Binafuxi Granules. Methods: The rat fever model induced by dry yeast was established, and the antipyretic mechanism of Binafuxi Granules on fungal fever rats was investigated by rat anal temperature measurement, ELISA detection, qPCR detection, and Western blot detection. Results: The dry yeast-induced fever model experiment showed that compared with the model group, the rectal temperature of rats in each administration group of Binafuxi Granules decreased significantly in a continuous period of time (P<0.01).Compared with the model group, the contents of interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in serum and the contents of prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) in hypothalamus were significantly decreased in each administration group (P<0.01).The mRNA expression levels of Toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), nuclear factor κB65 (NF-κB p65) and other immune and inflammatory response-related genes in the hypothalamus of rats were significantly inhibited (P<0.05).The expression levels of immune and inflammatory response-related proteins TLR4 and p-NF-κB65 in the hypothalamus of model rats were significantly down-regulated (P<0.05). Conclusion: Binafuxi Granules may inhibit the production of heat-causing inflammatory factors by regulating TLR4/NF-κB signaling pathway and exert antipyretic effect.

关键词

比那甫西颗粒 / 千酵母 / 解热作用 / 炎性因子 / 作用机制 / 信号通路

Key words

Binafusi Granules / dried yeast / antipyretic effect / inflammatory factors / mechanism of action / signaling pathway

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基金资助

新疆维吾尔自治区重大科技专项资助项目(2022A03008);拟上市中药民族药成果转化核心技术与关键技术突破研究资助项目(2022A03008-4)