Steiner A A, Colombari E, Branco L G
Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brasil.
Am J Physiol. 1999 Aug;277(2):R499-507. doi: 10.1152/ajpregu.1999.277.2.R499.
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 (T(b)) was measured in awake, unrestrained rats (basal T(b) = 36.8 +/- 0.2 degrees C). Intracerebroventricular injection of zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 75 nmol), a heme oxygenase inhibitor, caused no significant change in T(b), indicating that the central heme oxygenase pathway plays no tonic role in T(b) under the experimental conditions used. Intraperitoneal injections of LPS (50-100 microgram/kg) evoked dose-dependent increases in T(b). Intracerebroventricular injection of ZnDPBG in febrile rats attenuated LPS-induced fever (thermal index with ZnDPBG = 1.1 +/- 0. 2 degrees C, thermal index with vehicle = 2.3 +/- 0.4 degrees 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.
血红素加氧酶催化血红素代谢生成胆绿素、游离铁和一氧化碳（CO），CO已被证明是一种重要的神经调节因子。最近，有研究表明脂多糖（LPS）可诱导胶质细胞中的血红素加氧酶。因此，本研究旨在验证中枢CO在LPS诱导的发热中起作用这一假说。在清醒、不受限制的大鼠中测量结肠体温（T(b)）（基础T(b)=36.8±0.2℃）。脑室内注射血红素加氧酶抑制剂锌原卟啉-2,4-双乙二醇（ZnDPBG；75 nmol），T(b)无显著变化，表明在所采用的实验条件下，中枢血红素加氧酶途径对T(b)无调节作用。腹腔注射LPS（50 - 100微克/千克）可引起T(b)剂量依赖性升高。发热大鼠脑室内注射ZnDPBG可减轻LPS诱导的发热（ZnDPBG组热指数=1.1±0.2℃，溶媒组热指数=2.3±0.4℃），提示中枢血红素加氧酶途径在发热产生中起作用。脑室内注射血红素赖氨酸盐或CO饱和盐水可逆转ZnDPBG的解热作用。总体而言，我们的数据表明，血红素加氧酶产生的CO可能通过作用于中枢神经系统在发热产生中起重要作用。
