Carbon monoxide as a novel mediator of the febrile response in the central nervous system.

Carbon monoxide as a novel mediator of the febrile response in the central nervous system.
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一氧化碳作为中枢神经系统发热反应的新型介质。

DOI:
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发表时间:
1999
期刊:
American Journal of Physiology. Regulatory Integrative and Comparative Physiology
影响因子:
--
通讯作者:
L. Branco
L. Branco
中科院分区:
--
文献类型:
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作者:
A. Steiner;E. Colombari;L. Branco

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血红素加氧酶催化血红素代谢为胆绿素、游离铁和一氧化碳 (CO),已被证明是一种重要的神经调节剂。最近,已经证明脂多糖(LPS)可以诱导神经胶质细胞中的血红素加氧酶。因此,本研究旨在检验中枢 CO 在 LPS 引起的发热中发挥作用的假设。在清醒、不受约束的大鼠中测量结肠体温 (Tb)(基础 Tb= 36.8 ± 0.2°C)。脑室内注射血红素氧合酶抑制剂锌次卟啉2,4-双乙二醇(ZnDPBG;75 nmol),没有引起Tb的显着变化,表明在所用的实验条件下,中枢血红素氧合酶途径对Tb没有起到补益作用。腹腔注射 LPS (50-100 μg/kg) 会引起 Tb 的剂量依赖性增加。发热大鼠脑室内注射 ZnDPBG 可减轻 LPS 引起的发热(ZnDPBG 的热指数 = 1.1 ± 0.2°C,媒介物的热指数 = 2.3 ± 0.4°C),表明中枢血红素加氧酶途径在发热产生中发挥作用。脑室内注射血红素赖氨酸或 CO 饱和盐水可以逆转 ZnDPBG 的解热作用。总的来说,我们的数据表明,血红素加氧酶产生的一氧化碳可能通过作用于中枢神经系统在发烧产生中发挥重要作用。
Heme oxygenase catalyzes the metabolism of heme to biliverdin, free iron, and carbon monoxide (CO), which has been shown to be an important neuromodulatory agent. Recently, it has been demonstrated that lipopolysaccharide (LPS) can induce the enzyme heme oxygenase in glial cells. Therefore, the present study was designed to test the hypothesis that central CO plays a role in LPS-induced fever. Colonic body temperature (Tb) was measured in awake, unrestrained rats (basal Tb= 36.8 ± 0.2°C). Intracerebroventricular injection of zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 75 nmol), a heme oxygenase inhibitor, caused no significant change in Tb, indicating that the central heme oxygenase pathway plays no tonic role in Tb under the experimental conditions used. Intraperitoneal injections of LPS (50-100 μg/kg) evoked dose-dependent increases in Tb. Intracerebroventricular injection of ZnDPBG in febrile rats attenuated LPS-induced fever (thermal index with ZnDPBG = 1.1 ± 0.2°C, thermal index with vehicle = 2.3 ± 0.4°C), suggesting that the central heme oxygenase pathway plays a role in fever generation. The antipyretic effect of ZnDPBG could be reversed by intracerebroventricular administration of heme-lysinate or CO-saturated saline. Collectively, our data indicate that CO arising from heme oxygenase may play an important role in fever generation by acting on the central nervous system.
DOI: 10.1113/jphysiol.1985.sp015872
发表时间: 1985
期刊: The Journal of physiology
影响因子: --
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