1400W对内毒素血症猪呼出气一氧化氮及血浆硝酸盐水平的影响

Effects of selective iNOS inhibitor 1400W on expired nitric oxide and plasma nitrate concentration in a porcine model of endotoxemia

目的 探讨选择性诱导型一氧化氮合酶(iNOS)抑制剂1400W对内毒素血症猪一氧化氮产量的影响。方法猪14只,随机分为两组:内毒素组和1400W组。内毒素组持续静脉输注内毒素0.08mg·h-1,12 h后内毒素组继续输注内毒素,1400W组输注内毒素的同时输注1400W,1400W剂量为0.5 mg·kg-1·h-1,分别于输注内毒素前、输注后12 h及24 h测定呼出气一氧化氮含量、动脉和门静脉血浆硝酸盐浓度。结果 内毒素使呼出气一氧化氮含量、动脉和门脉血硝酸盐浓度明显升高,1400 W使呼出气一氧化氮含量降至基础水平(P<0.05),但对已升高的血浆硝酸盐浓度无逆转作用(P>0.05)。结论1400W通过抑制iNOS的活性,减少了内毒素血症时一氧化氮的合成和释放。

Objective To study the effects of selective inducible nitric oxide synthase (iNOS) inhibitor 1400W on nitric oxide (NO) exhalation and plasma nitrate concentration during endotoxemia in pigs. Methods Fourteen pigs of both sexes aged 12-16 weeks, weighing 40-60 kg were randomly divided into two groups : ( Ⅰ ) endotoxemia group ( n = 6) and ( Ⅱ ) 1400W group ( n = 8). The animals were anesthetized with pentobarbital and ketamine, intubated and mechanically ventilated. PaC02 was maintained at 35-45 mm Hg. Femoral artery and portal vein were cannulated for BP monitoring and blood sampling. E coli (LPS 20 mg L-1 ) was continuously infused iv at 4 ml h-1 for 24 h in both groups. In 1400W group, at 12 h of LPS infusion, continuous iv infusion of 1400W was started at 0.5 mg kg-1 h-1 . Blood samples were taken from artery and portal vein before LPS infusion (T0) and at 12 h (T, ) and 24 h (T2) of LPS infusion for determination of plasma nitrate concentration. Expired NO concentration was measured using NOA 280 NO analyzer. Results 1400W decreased LPS-induced increase in expired NO (P < 0.05), but could not reverse LPS-induced increase in arterial and portal venous nitrate concentration ( P > 0.05). Conclusion The selective iNOS inhibitor 1400W can inhibit iNOS activity and lead to decreased NO production.