预注不同剂量长托宁对内毒素休克兔肺动脉张力的影响及机制探讨

Effect of Preinjection of Different Doses of Penehyclidine Hydrochloride on the Pulmonary Artery Tension in Rabbits with Endotoxic Shock

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0.02 mg/kg+内毒素组(PHC2+L组),长托宁0.45mg/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15 min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,30 min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 (1)A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5 min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(0.02 mg/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NO含量有关,对肺循环有保护作用,而小剂量长托宁无此效应。

Objective To investigate the effect of different doses of penehyclidine hydrochloride（PHC） on pulmonary artery tension in rabbits with endotoxic shock and its mechanism.Methods Thirty New Zealand white rabbits were randomly divided into 5 groups（n =6 each group）：saline control group（group N）,acetylcholine control group（group A）,endotoxin control group（group L）,0.02 mg/kg PHC group（group PHC2＋L）,and 0.45 mg/kg PHC group（group PHC5＋L）.The rabbit model of endotoxic shock was established by injecting lipopolysaccharide（LPS） via internal jugular vein.PHC was injected 15 miniutes before the injection of LPS.The changes in mean arterial pressure were obversed,and the content of nitric oxide（NO） in pulmonary artery was detected.The rabbits were killed after 30 minutes,and the pulmonary arterial rings were isolated.The response of the vascular rings to acetylcholine was determined,and the half maximal effective concentration（EC50） was calculated.Results Acetylcholine induced pulmonary artery dilation in a dose-dependent manner in group A.Compared with group A,the pulmonary artery dilation significantly decreased and EC50 significantly increased in group L（P 0.01）.The content of NO increased 5 minutes after the injection of LPS in group L,and there was significant difference in NO content between groups L and A（P 0.01）.Preinjection of 0.45 mg/kg PHC inhibited the decrease of pulmonary artery dilation.The EC50 in group PHC5＋L was significantly lower than that in group L（P 0.01）,but there was no significant difference in EC50 between groups PHC5＋L and A.The above changes were not found in group PHC2＋L.Conclusion High dose,not low dose of PHC could reverse the acetylcholine-induced pulmonary artery dialtion in rabbit model of endotoxic shock,which may be related to the level of NO and has protective effect on pulmonary circulation.