- 作者: Shinn-Long Lin; Yen-Mei Lee; Hsin-Yi Chang; Yu-Wen Cheng; Mao-Hsing Yen
- 作者服務機構: 1 Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan; ; 2 Department of Pharmacology, National Defense Medical Center; ; 3 Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; ; 4 Department of Pharmacy, Taipei Medical University, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: 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-α 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-α levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.
- 中文關鍵字: --
- 英文關鍵字: hepatic dysfunction, naltrexone, nitric oxide, reactive oxygen species, sepsis, TNF-α