Division of Integrative Physiology, Department of Functional, Morphological and Regulatory Science, Tottori University Faculty of Medicine, Yonago, Tottori, Japan.
Eur J Appl Physiol. 2010 May;109(1):49-57. doi: 10.1007/s00421-009-1157-8. Epub 2009 Aug 23.
We investigated whether within the preoptic area, natriuretic peptide (NP) acts as an endogenous antipyretic in rats made febrile by systemic administration of bacterial endotoxin (lipopolysaccharide, LPS). Intravenous (i.v.) injection of LPS (2 microg/kg) induced a triphasic fever. The third phase of this fever was (a) significantly enhanced by an intrapreoptic (i.p.o.) injection of the NP-receptor (A-type and B-type) antagonist HS-142-1(1 microg), and (b) significantly attenuated by an i.p.o. injection of atrial NP (ANP, 20 ng). When given i.v., LPS induced significant upregulation of the mRNA coding for C-type NP within the anterior hypothalamus, and tended to upregulate that for ANP. The anterior hypothalamic expression of interleukin-1beta mRNA was significantly greater in rats injected i.v. with LPS than in saline-injected rats. These results suggest that NPs produced within the anterior hypothalamus after i.v. injection of LPS may act upon preoptic NP receptors to inhibit the LPS-induced fever, possibly through attenuation of the LPS-induced production of proinflammatory cytokines and/or the subsequent final fever mediator prostaglandin E(2).
我们研究了在给予内毒素（脂多糖，LPS）全身注射使大鼠发热的情况下，神经肽（NP）是否在前脑室内作为内源性解热物质发挥作用。静脉内（i.v.）注射 LPS（2μg/kg）可诱导三相发热。这种发热的第三相（a）可被前脑室内（i.p.o.）注射 NP 受体（A 型和 B 型）拮抗剂 HS-142-1（1μg）显著增强，（b）可被前脑室内注射心钠素（ANP，20ng）显著减弱。当静脉内给予 LPS 时，LPS 诱导了前下丘脑内编码 C 型 NP 的 mRNA 的显著上调，并且倾向于上调 ANP 的 mRNA。与盐水注射的大鼠相比，静脉内注射 LPS 的大鼠下丘脑前部的白细胞介素-1β mRNA 的表达显著增加。这些结果表明，LPS 静脉内注射后在前脑室内产生的 NPs 可能通过作用于前脑室内的 NP 受体来抑制 LPS 诱导的发热，可能通过减弱 LPS 诱导的促炎细胞因子的产生和/或随后的最终发热介质前列腺素 E2 来实现。
