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研究中枢 5-HT 受体在 LPS 诱导的发热模型中对扑热息痛解热作用机制中的可能作用。

The investigation of possible roles of central 5-HT receptors in antipyretic effect mechanism of paracetamol in LPS-induced hyperthermia model of mice.

机构信息

Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey.

Department of Pharmacology, Faculty of Pharmacy, Binali Yıldırım University, 24100, Erzincan, Turkey.

出版信息

Inflammopharmacology. 2019 Dec;27(6):1169-1178. doi: 10.1007/s10787-019-00617-1. Epub 2019 Jul 15.

Abstract

AIM

This study aimed to investigate the role of the 5-HT receptor in fever mechanisms and its possible effect on the antipyretic mechanism of paracetamol.

MATERIALS AND METHODS

The study consisted of eight experimental groups and one control group. Group I: healthy, II: LPS, III: LPS + PARA, IV: LPS + AGO, V: LPS + ANTA, VI: LPS + AGO + ANTA, VII: LPS + AGO + PARA, VIII: LPS + ANTA + PARA, and IX: LPS + AGO + ANTA + PARA. Rectal temperatures were measured with a rectal thermometer. At the end of the experiment, tissues were examined molecularly. Real-time PCR mRNA expression analyses were performed for the 5-HT7 receptor, IL-6, and TNF-α in hypothalamus tissue.

RESULTS

The mean differences in rectal temperature increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group and decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the healthy group. The IL-6 and TNF-α mRNA expression increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group in the 2nd and 4th hours. The IL-6 and TNF-α expression decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the LPS group in the 2nd and 4th hours. The 5-HT receptor mRNA expression increased in the LPS group when compared to the healthy group in the 2nd hour. The 5-HT receptor mRNA expression decreased in the LPS + AGO and LPS + AGO + PARA groups when compared to the LPS group in the 2nd hour. The 5-HT receptor mRNA expression increased the in LPS + ANTA and LPS + ANTA + PARA groups when compared to the LPS group in the 2nd hour.

CONCLUSION

The 5-HT receptor is a potential defense mechanism in stopping fever and the antipyretic property of paracetamol is not due to the 5-HT receptor.

摘要

目的

本研究旨在探讨 5-HT 受体在发热机制中的作用及其对扑热息痛解热机制的可能影响。

材料和方法

研究包括八个实验组和一个对照组。I 组:健康组;II 组:LPS 组;III 组:LPS+PARA 组;IV 组:LPS+AGO 组;V 组:LPS+ANTA 组;VI 组:LPS+AGO+ANTA 组;VII 组:LPS+AGO+PARA 组;VIII 组:LPS+ANTA+PARA 组;IX 组:LPS+AGO+ANTA+PARA 组。采用直肠温度计测量直肠温度。实验结束时,对组织进行分子水平检查。对下丘脑组织中的 5-HT7 受体、IL-6 和 TNF-α进行实时 PCR mRNA 表达分析。

结果

与健康组相比,LPS、LPS+ANTA 和 LPS+AGO+ANTA 组的直肠温度平均差异升高,而 LPS+PARA、LPS+AGO、LPS+AGO+PARA 和 LPS+AGO+ANTA+PARA 组的直肠温度平均差异降低。与健康组相比,LPS、LPS+ANTA 和 LPS+AGO+ANTA 组在第 2 小时和第 4 小时的 IL-6 和 TNF-αmRNA 表达增加。与 LPS 组相比,LPS+PARA、LPS+AGO、LPS+AGO+PARA 和 LPS+AGO+ANTA+PARA 组在第 2 小时和第 4 小时的 IL-6 和 TNF-α表达降低。与健康组相比,LPS 组在第 2 小时的 5-HT 受体 mRNA 表达增加。与 LPS 组相比,LPS+AGO 和 LPS+AGO+PARA 组在第 2 小时的 5-HT 受体 mRNA 表达降低。与 LPS 组相比,LPS+ANTA 和 LPS+ANTA+PARA 组在第 2 小时的 5-HT 受体 mRNA 表达增加。

结论

5-HT 受体是阻止发热的潜在防御机制,扑热息痛的解热作用不是由于 5-HT 受体。

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