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抗氧化剂抑制内毒素性休克大鼠诱导型一氧化氮合酶基因表达

Antioxidant inhibits gene expression of inducible nitric oxide synthase in rat septic shock
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摘要 感染性休克时循环机能障碍的显著特点表现为进行性、顽固性低血压,伴对血管活性药物敏感性降低,以至组织器官灌注不足、重要器官机能代谢障碍,病死率仍高达30%~70%。休克时循环机能障碍所涉及的病理生理机制极其复杂,脂质过氧化物的堆积和NO的爆发生成是其中的关键病理因素之一。我们以往的研究中发现抗氧化剂能部分逆转内毒素休克大鼠的血管低反应性,为了进一步探讨其治疗学机制,本实验对抗氧化剂在内毒素性休克大鼠iNOS mRNA表达中的作用进行了观察。 Objective To study the effect of antioxidant on mRNA expression of inducible nitric oxide synthase (iNOS) in septic shock rat and its possible therapeutic mechanism. Methods Forty male SD rats weighting (200 -250) g were randomly divided into 5 groups(n =8 in each group) : group Ⅰeontrol; groupⅡseptic shock ( LPS 15 mg · kg^-1 iv) ; groupⅢ septic shock + propolol (at 1 h after LPS, propofol 10 mg · kg^-1 iv, then continuous infusion of propofol 10 mg· kg^-1 · h^-1 ) ; group Ⅳ septic shock + uric acid (at 1 h after LPS, uric acid 200 mg · kg^-1 ip) and groupⅤseptie shock + mclatonin (at 1 h after LPS, melatonin 10 mg· kg^-1 ·ip). The plasma malondialdehyde (MDA) and nitrate/nitrite concentration were assayed in all groups at 6 h after LPS administration. Then iNOS mRNA expression in aorta, vein, heart, liver, lung and kidney were measured by reverse transcription polymerase chain reaction (RT -PCR). Results The plsma MDA and nitrate/ nitrite concentrations were significantly higher in LPS group compared with the control group( P 〈 0.01 ). In all of the three treated groups, plasma MDA and nitrate/nltrite concentrations were lower than in the LPS group(P 〈 0.05). The mRNA of iNOS in all of the organs was strongly up-regulated after injection of LPS( P 〈 0.01 ). In all three treated groups, however, iNOS mRNA expressions in organs were downregulated significantly eompa,ing with the LPS group (P 〈 0, 05 ). Conclusion Circulation disfunction in septic shock is related to the up -regulation of iNOS mRNA expression and the over production of nitric oxide (NO) and lipid peroxidation. The therapeutic effects of antioxidants on the vascular hyporeactivity of septic shock is related to depress the over expression of iNOS mRNA and decrease the peroxide production.
作者 景亮 廖丽君
出处 《国际麻醉学与复苏杂志》 CAS 2006年第1期4-6,共3页 International Journal of Anesthesiology and Resuscitation
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