异丙酚对内毒素性休克大鼠血管反应性的影响

Effect of propofol on vascular reactivity in rat septic shock

目的评价异丙酚对内毒素性休克大鼠血管反应性的影响。方法40只雄性SD大鼠随机分为4组(n=10),对照组;休克组:静脉注射内毒素(LPS)15 mg·kg-1;异丙酚组:静脉注射LPS 后1 h,静脉注射异丙酚10 mg·kg-1后10 mg·kg-1·h-1持续静脉泵注4 h;5-甲氧色胺组:静脉注射LPS 后1 h,腹腔注射5-甲氧色胺10 mg·kg-1。注射LPS后6 h,各组大鼠依次静脉注射去氧肾上腺素(PE) 0.5、1、2、2.5 μg·kg-1,记录注药后平均动脉压(MAP)的增幅百分比。注射LPS后6 h,经心内穿刺取血, 测定血浆丙二醛(MDA)及一氧化氮浓度(NO2-/NO3-)。所有在体实验结束后取大鼠胸主动脉环做离体张力实验,建立去氧肾上腺素的剂量-张力反应曲线,并计算相应主动脉环最大收缩张力(Emax)、半数有效浓度(EC50)。结果休克组、异丙酚组、5-甲氧色胺组MAP增幅百分比均低于对照组(P< 0.05),异丙酚、5-甲氧色胺组MAP增幅百分比均高于休克组(P<0.05)。异丙酚组、5-甲氧色胺组血浆MDA及NO2-/NO3-浓度均低于休克组(P<0.05)。在离体实验中,休克大鼠主动脉环对PE反应的Emax及EC50与均低于对照组(P<0.05),但是异丙酚组和5-甲氧色胺组主动脉环对PE的反应均升高(P<0.05)。异丙酚组和5-甲氧色胺组主动脉收缩力均高于休克组,并且主动脉环对PE的Emax增高,EC50降低(P<0.05)。结论异丙酚可能通过减少氧自由基,抑制NO的合成,从而改善内毒素性休克大鼠的血管低反应性。

Objective To study the effect of prepoful on vascular reactivity and plasma malondialdehyde（MDA） and nitric oxide （NO） in septic shock.Methods Forty male SD rats weighing 200-250 g were randomly divided into 4 groups （n = 10 in each group）： group Ⅰ control; group Ⅱ septic shock; group Ⅲ septic shock ＋prepofol and group Ⅳ septic shock ＋ melatonin. The animals were anesthetized with intraperitoneal pentobarbital 40 mg· kg^-1. The femoral artery and vein were connulated for MAP monitoring and drug administration. The animals were breathing spontaneously. Septic shock was induced by intravenous LPS 15 mg·kg^-1. In group m a bolus of propoful 10 mg·kg^-1 was given i.v. at 1 h after intravenous LPS followed by intravenous propofol infusion at 10 mg· kg^-1·h^-1. In group Ⅳ melatonin 10 mg was given intraperitoneally at lh after LPS i.v. , Six hours after LPS administration 4 doses of phenylephrine （PE） 0.5, 1, 2, 2.5 μg· kg^-1 were given i.v. in succession. The next dose was given when MAP returned to the baseline level after previous PE. The percent change in MAP after each dose was recorded. Blood samples were taken at 6 h after LPS administration for determination of plasma MDA and NO concentrations. After the in vivo experiment the animals were sacrificed and thoracic aortas were removed and cut into segments of 3 nun in length which were bathed in Krebs buffer aerated with 95% O2 and 5% CO2 at 37℃ . The aortic rings were stretched to a resting tension of 2.0 g. The segments were then exposed to increasing concentrations of PE （from 1 nmol· L^-1 to 30 μmol· L^-1）, The dose-respouse curves were obtained. Emax and EC50 were calculated, Results The percent increase in MAP induced by PE was significantly reduced by septic shock （group Ⅱ ,Ⅲ, Ⅳ ） as compared with control group （ Ⅰ ）, but was significantly larger in propofol and melatonin groups （ Ⅲ ,Ⅳ ） than in group Ⅱ In the in vitro experiment the maximum response to PE and EC50 were significantly reduced in rats with septic shock as compared with rats in control group （ P 〈 0.05） but the reactivity of aorta to PE was significantly improved by propofol and melatonin （ P 〈 0.05）. The plasma MDA concentration and nitrate/nitrite were much lower in propofol and melatonin groups （ Ⅲ , Ⅳ ） than in septic shock group （ Ⅱ ）.Conclusion Propofol effectively improves vascular reactivity in septic shock by reducing oxygen free radicals and inhibiting nitric oxide synthesis.