摘要
目的探讨允许性高碳酸血症对大鼠脑缺血再灌注损伤的影响。方法健康雄性Wistar大鼠40只,随机分为5组（n=8）,假手术组（SH组）、脑缺血再灌注组（IR组）、PaCO2 60～80 mm Hg组（P1组）、PaCO281～100 mmHg组（P2组）和PaCO_2 101～120mmHg组（P3组）。采用双侧颈总动脉夹闭并发低血压法建立脑缺血再灌注模型。P1组、P2组和P3组于再灌注同时吸入CO2 2h,使PaCO2分别维持在各组相应PaCO2允许范围内。再灌注24h时行神经功能缺陷评分,观察海马超微结构,测定海马超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量、caspase-3活性以及caspase-3蛋白表达。结果与SH组比较,其余4组再灌注24h时神经功能缺陷评分升高,超微结构损伤加重,SOD活性降低,MDA含量、caspase-3活性升高,caspase-3酶原蛋白表达下调,其裂解片断表达上调;与IR组和P3组比较,P1组和P2组神经功能缺陷评分降低,超微结构损伤减轻,SOD活性增加,MDA含量、caspase-3活性降低,caspase-3酶原蛋白表达上调,其裂解片断表达下调;与P1组比较,P2组超微结构损伤减轻,SOD活性增加,MDA含量、caspase-3活性降低,caspase-3酶原蛋白表达上调,其裂解片断表达下调。结论允许性高碳酸血症PaCO2在一定范围内（60～100mmHg）可减轻大鼠脑缺血再灌注损伤,PaCO281～100mmHg时脑保护作用较好,其机制与减轻氧化应激反应,降低caspase-3活性有关。
Objective To investigate the effects of permissive hypercapnia on cerebral ischemiareperfusion （I/R） injury and the underlying mechanism. Methods Forty male Wistar rats weighing 300-350 g were randomly divided into 5 groups （ n = 8 each） ： group Ⅰ sham operation; group Ⅱ cerebral I/R; group Ⅲ and Ⅴ inhaled CO2 for 2 h to keep PaCO2 within the range of 60-80 nnn Hg （P1）, 81-100 inin Hg （P2） and 101-120 inin Hg （P3） from the beginning of reperfusion. Cerebral I/R was produced by occlusion of bilateral common carotid arteries combined with controlled hypotension （MAP = 30-40 inin Hg） for 15 inin. The neurologic deficit was evaluated and scored according to Brambrink AM et al at the end of 24 h repeffusion. The animals were then killed. Their brains were immediately removed and bilateral hippocainpi isolated for examination of pathologic changes with electron inicroscope and determination of SOD and caspase-3 activity, MDA content and caspase-3 protein expression. Results In I/R group the neurologic deficit scores were significantly increased; there was serious damage to the structure of hippocampus; the MDA content and caspase-3 activity were significantly increased while SOD activity was significantly decreased; the expression of pro-caspase-3 was significantly decreased and the cleavage of pro-caspase-3 increased after 24 h reperfusion as compared with sham operation group （P 〈 0.01 ）. The above-mentioned cerebral I/R-induced changes were significantly ameliorated in group PI and P2 and group P2 provided greater degree of protection than group P1 . Conclusion Hypercapnia within the range of 60-100 mm Hg can attenuate the cerebral I/R-induced injury by reducing oxidative response and caspase-3 activity.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2007年第11期1025-1029,共5页
Chinese Journal of Anesthesiology
基金
黑龙江省自然科学基金重点项目（ZJY0607-01）
哈尔滨医科大学研究生创新基金
关键词
高碳酸血
再灌注损伤
脑
Hypereapnia
Reperfusion injury
Brain
