比较枕大池注入不同剂量利多卡因对蛛网膜下腔出血的脑保护效应

Comparative neuroprotection of different-dose Lidocaine by injecting into in a rabbit model of subarachnoid hemorrhage

目的比较枕大池注入不同剂量的利多卡因对蛛网摸下腔出血的脑保护作用,确定最佳的利多卡因枕大池注入剂量。方法56只新西兰大白兔随机分为假手术组(sham)、蛛网膜下腔出血组(SAH)、利多卡因1mg组(LD1)、利多卡因2mg组(LD2)、利多卡因4mg组(LD4)、利多卡因6mg组(LD6),假手术组6只,其余每组10只。各组动物均在全麻下行手术操作,出血组和各利多卡因治疗组的动物取自体动脉血1.5mL注入枕大池,而假手术组注入1.5mL生理盐水。半小时后假手术组和出血组的动物再次从枕大池注入0.3mL生理盐水,各治疗组(C-F)分别注入2%的利多卡因0.05、0.1、0.2、0.3mL。72h后取脑基底动脉以及海马组织行病理检查测定血管管腔面积和直径、海马正常神经元密度、c-fos阳性细胞数目。结果蛛网膜下腔出血组的海马正常神经元密度比假手术组及各治疗组的低,而海马c-fos阳性细胞比假手术组及各治疗组的多(P<0.05、P<0.01或P<0.001);蛛网膜下腔出血组脑基底动脉的直径及管腔面积比假手术组及各治疗组的小(P<0.05或P<0.01)。各个治疗组之间的神经元密度以及c-fos阳性细胞比较差异无统计学意义,LD6组的基底动脉直径和管腔面积比LD1组的大(P<0.05)。结论枕大池给不同剂量利多卡因对蛛网膜下腔出血均有不同程度的脑保护作用,LD6组的保护作用可能会更好。

Objective We would compare the neuroprotection of different - dose Lidoeaine by injecting Lidocaine into cisterna magna in a rabbit model of subarachnoid hemorrhage,and decided the optimal dose of Lidocaine for injection into cisterna magna. Methods Fifty - six New Zealand white rabbits were randomly divided into sham group（ n =6） , subarachnoid hemorrhage（SAH） group（ n = 10）, Lidocaine 1 mg group （LDI,n = 10） ,2 mg group （ LD2,n = 10） , 4 mg group（ LD4,n = 10） ,6 mg group （LD6 ,n = 10）. All animals undergo operation under general anaesthesia. 1.5 mL autologous nonheparinized arterial blood was injected into cisterna magna in SAH and every Lidocaine group, and 1. 5 mL saline into cisterna magna in sham group respectively. Thirty minutes after SAH 0. 3 mL saline was injected into cisterna magna in sham and SAH group, and 0. 05,0. 1,0. 2,0. 3 mL 2 percent Lidocaine into cisterna magna in LD1 ,LD2,LD4,LD6 group, respectively. 72 hours after SAH all animals were deeply anesthetized and killed by perfusion -fixation. Their basilar arteries and hippocampus tissue were processed for morphometric analysis. Datum were presented as means ＋ SD, which were analyzed by ANOVA. P 〈0. 05 was considered statistically significant. Result The normal neuron density of hippocampus were lower in SAH group than that of the other five groups, and had more cells of expressing c - fos in hippocampus in SAH group than the other five groups（ P 〈0.05, P 〈0. O1 or P 〈0. 001 ）. The cross - section areas and diameter of basal arteries were smaller in SAH group than that of the other three groups （ D - F） （P 〈0. 05 or P 〈0. 01 ）. It was not statistically significant between four Lidocaine groups for the normal neuron density of hippocampus and cells of expressing c - fos in hippocampus. The cross - section areas and diameter of basal arteries in LD6 group were bigger than that of LD1 group （ P 〈 0. 05 ）. Conclusions Cisternal delivery of different - dose Lidocaine can produce different degree neuroprotection. 6 mg Lidocaine maybe has more prominent neuroprotection.