亚低温联合尼莫地平对兔全脑缺血再灌注损伤的保护

目的 探讨亚低温及尼莫地平对脑缺血再灌注损伤的保护作用及机制.方法 健康新西兰大耳白兔24只,随机分为健康对照组(Ⅰ组)、常温缺血再灌注损伤组(Ⅱ组)、亚低温缺血再灌注损伤组(Ⅲ组)、亚低温+尼萸地平组(Ⅳ组),每组6只.采用双侧颈总动脉夹闭低血压脑缺血模型,除健康对照组外,各组均行脑缺血30 min,再灌注3 h;Ⅲ组在双侧颈总动脉夹闭的同时行局部脑组织亚低温处理,Ⅳ组在夹闭的同时行局部脑组织亚低温+尼萸地平10μg·kg-1·h-1静脉输注并维持至再灌注后3 h.常规监测鼓膜温度、创伤性平均动脉压(MAP)和中心静脉压(CVP).分别于缺血前、缺血30 min、再灌注30、60、120、180 min采血标本,血气分析仪检测颈静脉血氧饱和度(SjvO2).再灌注3 h后处死动物,取脑称干湿重比计算脑含水量.ELISA方法检测血清烯醇化酶(NSE)含量.结果 脑含水量Ⅱ组>Ⅲ组>Ⅳ组.Ⅱ组全脑缺血冉灌注后60 min,血清NSE含量明显升高至(14.07±0.67)μg/L,120 min达高峰(18.53±0.85)μg/L,而SjvO2降低至(66±7.6)%.Ⅲ组冉灌注60min时血清NSE含量下降至(7.27±0.25)μg/L;180 min时至(9.17±0.57)μg/L,SjvO2升高至(91±4.5)%,与Ⅱ组比较差异有统计学意义(P均<0.01).Ⅳ组的血清NSE含量显著低于Ⅲ组,差异具有统计学意义.再灌注30 min,颈静脉血氧饱和度升高,Ⅲ组与Ⅳ组差异无统计学意义(P>0.05).结论 局部脑组织亚低温联合尼莫地平静脉输注能显著减少兔全脑缺血再灌注后血清NSE表达,升高SjvO2,减轻缺血再灌注损伤所致的脑水肿.

Protection effect of local cerebral sub-hypothermia combined with nimodipine injection on the global cerebral ischemic/reperfusion injury in rabbits

Objective To explore the protection effect and mechanism of sub-hypothermia combined with nimodipine injection on global cerebral ischemic/repeffusion (I/R) injury. Methods Twenty-four healthy New Zealand rabbits were randomly divided into normal control group (group Ⅰ) ,normal thermal I/R group (group Ⅱ), sub-hypothermia I/R group (group Ⅲ), sub-hypothermia combined with nimodipine injection I/R group(group Ⅳ). The model was established by bilateral common carotid arteries occlusion for 30 min combined with systemic hypotension. Except the normal control group,the rabbits underwent ischemia for 30 min and were reperfused for 3 hours. Local cerebral sub-hypothermal was given to group Ⅲ at the same time of ischemia and reperfusion for 3 hours. The local cerebral sub-hypothermal combined with 10 μg·kg-1·h-1 nimodipine intravenous injection was given to group Ⅳ. The temperature of the tympanic membrane, mean arterial pressure(MAP) and central venous pressure(CVP) were routinely recorded. Artery blood and oxygen saturation of jugular vein(SjvO2) were detected before ischemia, ischemia for 30 min, reperfusion for 30,60, 120,180 min. Cerebral water contant was calculated after sacrifice of rabbits. ELISA method was used to detect the content of serum neurons specific enolase(NSE). Results The water content was highest in group Ⅱ, and lowest in group Ⅳ. The content of NSE was increased significantly after reperfusion for 60 min[(14.07±0.67) μg/L] ,and reached the highest level after reperfusion for 120 min[(18.53±0.85)μg/L], but the SjvO2 was reduced[(66±7.6)%]. The content of serum NSE was reduced after reperfusion for 60 min[(7. 27±0.25) μg/L] and for 180 min by sub-hypothemia treatment [(9.17±0.57) μg/L], compared with group Ⅱ ,the difference was significant(all P<0.01). The decreased level of the serum NSE was more significant in group Ⅳ than that in group Ⅲ. However ,the difference of increased SjvO2 was not significant between these two groups after reperfusion for 30 min (P>0.05). Conclusion The local cerebral sub-hypothermia combined with nimodipine intravenous injection can significantly reduce the serum NSE content, increase the SjvO2, and attenuate the cerebral edema after I/R injury in rabbit.