Lin Shinn-Long, Lee Yen-Mei, Chang Hsin-Yi, Cheng Yu-Wen, Yen Mao-Hsiung
Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan.
J Biomed Sci. 2005;12(2):431-40. doi: 10.1007/s11373-005-0647-x.
Naltrexone, an opioid antagonist, has been reported to possess an anti-inflammatory effect via blockade of opioid receptor. The aim of this study is to evaluate the protective effect of naltrexone on LPS-induced septic shock in rats. Sepsis was induced by administration of LPS (10 mg/kg, i.v.) in anesthetized rats. Results demonstrated that pretreatment with naltrexone (10 mg/kg, i.v.) significantly ameliorated hypotension and bradycardia of rats 6 h after LPS administration. In isolated blood vessel, study showed that pretreatment with naltrexone significantly improved norepinephrine-induced vasoconstriction and ACh-induced vasorelaxation in aorta of endotoxemic animals. Naltrexone significantly reduced the elevation of serum glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase (as index of hepatic function) induced by LPS. The infiltration of polymorphonuclear neutrophils into liver 48 h after LPS treatment in mice was also reduced by naltrexone. On the other hand, naltrexone significantly decreased the levels of plasma TNF-alpha and inhibited overproduction of superoxide anions in aortic rings. However, naltrexone did not suppress the overproduction of NO (measured by its metabolites nitrite/nitrate in plasma) and iNOS expression in lungs induced by LPS. In in vitro study, naltrexone did not attenuate non-enzymatic iron-induced lipid peroxidation in rat brain homogenates. In conclusion, pretreatment with naltrexone significantly improved circulatory failure and hepatic dysfunction in sepsis. These effects were associated with reduction of TNF-alpha levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.
纳曲酮是一种阿片类拮抗剂，据报道可通过阻断阿片受体发挥抗炎作用。本研究旨在评估纳曲酮对脂多糖（LPS）诱导的大鼠脓毒症休克的保护作用。在麻醉大鼠中通过静脉注射LPS（10mg/kg）诱导脓毒症。结果表明，用纳曲酮（10mg/kg，静脉注射）预处理可显著改善LPS给药6小时后大鼠的低血压和心动过缓。在离体血管研究中，表明用纳曲酮预处理可显著改善内毒素血症动物主动脉中去甲肾上腺素诱导的血管收缩和乙酰胆碱诱导的血管舒张。纳曲酮显著降低了LPS诱导的血清谷氨酸草酰乙酸转氨酶和谷氨酸丙酮酸转氨酶（作为肝功能指标）的升高。纳曲酮还减少了LPS处理小鼠48小时后肝脏中多形核中性粒细胞的浸润。另一方面，纳曲酮显著降低了血浆肿瘤坏死因子-α（TNF-α）水平，并抑制了主动脉环中超氧阴离子的过量产生。然而，纳曲酮并未抑制LPS诱导的肺中一氧化氮（通过其血浆代谢产物亚硝酸盐/硝酸盐测量）的过量产生和诱导型一氧化氮合酶（iNOS）的表达。在体外研究中，纳曲酮并未减弱非酶铁诱导的大鼠脑匀浆脂质过氧化。总之，用纳曲酮预处理可显著改善脓毒症中的循环衰竭和肝功能障碍。这些作用与TNF-α水平降低和超氧阴离子形成减少有关，这可能归因于阿片受体的拮抗作用。
