预注不同剂量长托宁对内毒素休克兔肺动脉张力影响及机制探讨

 目的 探讨预注不同剂量长托宁对内毒素休克兔肺动脉张力影响及机制。方法 　新西兰大白兔 30只 ,随机分为5组: 生理盐水对照组（N组），乙酰胆碱对照组(A组) ，内毒素对照组(L组)，长托宁0.02mg/kg+内毒素组(PHC2+L组) ，长托宁0.45 mg/kg+内毒素组(PHC5+L组) 。L组经颈静脉注入内毒素（LPS)复制兔内毒素休克模型 ，PHC2+L组、PHC5+L组分别在LPS注入前15min注入长托宁，动态监测体循环平均动脉压力(MAP)，取颈动脉血样检测肺循环一氧化氮（NO）含量，30min后动物处死，心肺联合取出，制备肺动脉环，应用血管张力测定技术测血管环对乙酰胆碱（Ach）张力反应，并计算Ach曲线的半数有效浓度(EC50)。 结果　①A组加入Ach后可剂量依赖性引起肺动脉舒张；②与A组比较，L组可明显降低Ach引起的舒张反应、EC50增大（P<0．01）；同时检测到肺循环NO含量于LPS后5min开始持续性增多，较A组均有显著性差异（P<0．01）；③预注入大剂量长托宁（0.45 mg/kg）能逆转L组舒张反应的下降、EC50较L组减小（P<0．01），与A组无差异（P>0.05），此作用与肺循环NO含量有关；而小剂量长托宁（0.02mg/kg）无此作用。结论 　大剂量长托宁能逆转内毒素休克兔肺动脉对Ach的舒张反应的降低，此作用与肺循环N0含量有关，对肺循环有保护作用，而小剂量长托宁无此效应。

Effect of preinjection of Penehyclidine Hydrochloride in different doses on the Tension of pulmonary artery in rabbits with endotoxic shock

Objective To investigate the effect of penehyclidine hydrochloride in different dose on the tension of pulmonary artery in rabbits with endotoxic shock and its mechanism.Methods Thirty newzland white rabbits were divided into five groups randomly: saline control group, acetylcholine control group，endotoxin shock control group，penehyclidine hydrochloride（0.02mg/kg）group；penehyclidine hydrochloride (0.45 mg/kg)group. LPS was injected to rabbits to build the model of endotoxin shock,and PHC was preinjected fifteen miniutes ago before LPS administration.The changes of mean arterial pressure(MAP) was obversed ,and nitric oxide in pulmonary arteries were recorded ,too.Then the rabbits were killed to make pulmonary arterial rings after thirty minutes .Pulmonary artetial reactivities to Ach was served by isolated arterial ring technique.Results ① Pulmonary arteries were inhibited the effect of dose-dependent relaxation by Ach in group A ; ②Compared to group A , the relaxation response to Ach was depressed significantly after LPS was injected，and EC50 was enhanced（P<0．01）;NO in pulmonary circulation were increased dramatically after five minutes when LPS was injected（P<0．01）；③But the effect could be reversed by preinjection of high dose of penehyclidine hydrochloride（0.45 mg/kg）,and EC50 was decreased（P<0．01）；NO in pulmonary circulation might contribute to the effect；while low dose of penehyclidine hydrochloride （0.02mg/kg）did not have the effect.Conclusion High dose of had protective effects on pulmonary circulation in rabbits with endotoxin shock，and the advanced effect was brought about by reversing the relaxation response to Ach on pulmonary arteries through NO after injection of LPS .