尤瑞克林对心脏骤停后综合征兔脑保护作用的研究

Brain Protective Effects of Urinary Kallidinogenase in Rabbits with Post-cardiac Arrest Syndrome

目的:探讨尤瑞克林(UK)对心脏骤停后综合征(PCAS)兔脑的保护作用及机制。方法:将42只日本大耳白兔随机分为假手术组(n=6)、PCAS组(n=12)、UK大剂量(UK-H)组(n=12)、UK小剂量(UK-L)组(n=12)。采用窒息性心脏骤停法制备兔PCAS模型,假手术组不造成窒息。复苏成功后UK-H、UK-L组立即给予UK 17.5×10^(-3)PNAU/kg、3.5×10^(-3)PNAU/kg,PCAS组注射等量生理盐水。分别于复苏前、复苏后6 h、24 h、48 h检测血清神经元特异性烯醇化酶(NSE),并进行神经功能缺损评分。48 h后取兔脑组织,应用Western blot方法测定脑组织Caspase-3、Caspase-9表达。结果:与假手术组比,PCAS组、UK-H组、UK-L组血清NSE水平在复苏后6 h、24 h、48 h均明显升高(P<0.01)。与PCAS组比,UK-H组、UK-L组血清NSE水平、神经功能损伤评分在复苏后24 h、48 h明显减少,复苏后48 h Caspase-3、Caspase-9表达水平减低(P<0.05),且在复苏后48 h UK-H组较UK-L组减低更为明显(P<0.05)。结论:UK能减少复苏后脑炎性因子表达,改善神经功能,其机制可能与抑制细胞凋亡有关。

Objective： To investigate the brain protective effects and mechanism of urinary kallidinogenase（UK） in rabbits with post-cardiac arrest syndrome（PCAS）. Methods： Japanese white rabbits were random divided into the sham group（n=6）, PCAS group（n=12）, UK high-dose group（UK-H group, n=12）, and UK low-dose group（UK-L group, n=12）. PCAS models were established by using asphyxia-induced cardiac arrest;the sham group was not subjected to asphyxia. Immediately after ROSC, UK-H and UK-L groups were given 17.5×10^-3 PNAU/kg and 3.5×10^-3 PNAU/kg doses of UK, and the PCAS group was injected with an equal amount of saline. Serum level of neuron specificity enolization enzyme（NSE） was examined before ROSC and 6 h, 24 h,and 48 h after ROSC respectively. Functional outcomes were measured by neurological deficit score. Rabbit brain tissue was collected after 48 h, and Western blot was performed to determine brain tissue Caspase-3 and Caspase-9 expression. Results： Compared to the sham group,serum level of NSE was significantly elevated in the PCAS group, UK-L group, and UK-H group 6 h, 24 h, and 48 h after ROSC（P〈0.01）. Compared to PCAS group,serum level of NSE and neurological deficit score was clearly decreased in the UK-L group and UK-H group 24 h and 48 h after ROSC; the expression level of Caspase-3 and Caspase-9 was significantly attenuated in the two groups 48 h after ROSC（P〈0.05）, with the UK-H group showing a greater reduction than the UK-L group（P〈0.05）. Conclusion： UK reduced brain inflammation and alleviated neurological deficit, and the mechanism may be related to inhibition of apoptosis.