允许性高碳酸血症对大鼠脑缺血再灌注时脑水肿的影响

Effects of permissive hypercapnia on brain edema induced by ischemia-reperfusion in rats

目的探讨允许性高碳酸血症对大鼠脑缺血再灌注时脑水肿的影响。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 60～80mmHg组（P1组）、PaCO2 81～100mmHg组（P2组）和PaCO2 101～120mmHg组（B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损伤模型。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时处死大鼠，测定脑水含量和海马水通道蛋白（AQP）-4表达。结果与SH组比较，其余4组脑水含量及AQP-4表达升高（P〈0．01）；与IR组、P1组和P2组比较，P3组脑水含量及AQP-4表达升高（P〈0．01）；与IR组比较，P1组和P2组AQP-4表达下调（P〈0．05）。结论允许性高碳酸血症PaCO2 101～120mmHg可加重大鼠脑缺血再灌注时脑水肿的程度，可能与其上调AQP-4表达有关；而PaCO2 60—100mmHg时不加重脑水肿的程度。

Objective To investigate the effects of permissive hypercapnia on brain edema induced by cerebral ischemia-reperfusion （I/R） .Methods Forty male Wistar rats weighing 300-350 g were randomly divided into 5 groups （ n = 8 each） ： group Ⅰ sham operation （S） ; group Ⅱ cerebral I/R; group Ⅲ , Ⅳ, Ⅴ inhaled CO2 for2 h to keep PaCO2 at 60-80 mm Hg （P1）, 81-100 mm Hg （P2） and 101-120 mm Hg （P3） respectively, starting from the beginning of reperfusion. Cerebral I/R was produced by occlusion of bilateral common carotid arteries combined with controlled hypotension （MAP = 30-40 mm Hg） for 15 min. The animals were killed at the end of 24 h reperfusion. Brains were immediately removed for determination of brain water content and expression of aquaporin4 （AQP-4） in hippocampus. Results The brain water content and AQP-4 protein expression in the hippocampus were significantly increased after 24 h reperfusion in group Ⅱ - Ⅴ as compared with control group （S）, and were significantly higher in groupV （P3） than in group Ⅱ （I/R）, Ⅲ （P1） and Ⅳ （P2） . The AQP-4 expression was significantly lower in group Ⅲ and Ⅳ than in group Ⅴ. Conclusion Hypercapnia within the range of 60-100 mm Hg does not accentuate brain edema induced by cerebral I/R while hypercapnia at 101-120 mm Hg can aggravate brain edema and up-regulate AQP-4 protein expression in the brain.