大剂量HBO治疗急性脑卒中的疗效及对氧化应激的影响

Effect of Large Dose Hyperbaric Oxygenation on Oxidative Stress and on Outcome of Acute Ischemic Stroke

目的评估2种大剂量高压氧(hyperbaric oxygenation,HBO)超早期治疗急性脑卒中的疗效及对氧化应激的影响。方法以雄性大鼠大脑中动脉永久性阻塞模型为对象,以神经功能评分和梗死容积测定为疗效评估指标,以缺血脑组织SOD(超氧化物歧化酶)、MDA(丙二醛)和NO(一氧化氮)水平变化为氧化应激观察指标,对持续9h和18h2种HBO方案超早期治疗急性缺血性脑卒中24h至5d的疗效及18h至5d不同时间点对氧化应激的影响进行研究。结果①HBO组各时间点神经功能评分明显好于对照组(P<0.01),5d时梗死容积比对照组显著降低(P<0.01);②9hHBO组疗效优于18hHBO组疗效,但差异无统计学意义;③18hHBO组18h和48h时SOD水平较对照组水平降低,差异有统计学意义(P<0.01和P<0.05);④HBO组各时间点缺血脑组织MDA均低于对照组相应时间点水平,尤以18h为著(P<0.05);⑤HBO组缺血脑组织18h和48h时NO含量均显著高于对照组相应时间点(P<0.01),其中,18h组18h时缺血脑组织NO含量显著高于9h组(P<0.05),5d时3组NO含量基本持平。结论①持续9h和18hHBO超早期治疗急性缺血性脑卒中可显著降低梗死容积,改善神经功能预后;②HBO超早期治疗急性脑卒中的剂量不是越大越好,过大剂量可能会加重过氧化损伤。

Objective To evaluate the therapeutic efficacy of two kinds of large dose hyperbaric oxygenation protocol on superearly acute permanent middle cerebral artery occlusion and their effects on oxidative stress of ischemic brain tissue in rats. Methods Rat＇ s intraluminal middle cerebral artery permanent occlusion models（MCAO） were randomly divided into two HBO groups（9 h and 18 h） and a control group. Main Outcome Measures： 1 ） The Garcia neurological grading systems were used to assess the therapeutic efficacy of HBO. 2） Twenty-four hours and 5 days after MCAO, the infarct volume was calculated with the TI＇C pathological staining and NIH Image J software. 3） The animals of the three groups were separately examined for SOD, MDA and NO levels of ischemic brain tissue at the 18 h, 48 h and 5 day with spectrophotometric device. Results 1 ） There was significant improvement in neurobehavioral outcome of rats in 9 h and 18 h groups compared with the control group（ P 〈 0.01 ）. 2） Cerebral infarct volume decreased 63% ～ 64% in rats of 9 h group and 66% ～ 51% in rats of 18 h group respectively at 24 h and 5 d compared with the control group. 3 ） The SOD level of 18 h group was remarkably lower than that of the control group at 18 h and 48 h （ P 〈 0.01 and P 〈 0.05 respectively ）. 4 ） The MDA level of the 9 h and 18 h groups were both remarkably lower than the controls, especially at the 18 h point（ P 〈 0.05 ）. Meanwhile, the level of the 9 h group was remarkably lower than both of the 18 h group and the control group（P 〈0.01 ＆ P〈0.05 respectively）. 5） The levels of NO in both HBO groups were remarkably higher than that of the control at 18 h and 48 h time points（ P 〈0.01 ） ; while the level in 18 h group was remarkably lower than that of 9 h group at 18 h time point（P 〈0.05）. On the 5th day, the levels of NO were basically the same in all three groups. Conclusion 1 ） The two kinds large dose HBO is highly efficient in reducing infarct volume and improving neurobohavioral outcome in permanent middle cerebral artery occlusion at super-early stage. 2） The dosage of HBO is not the longer the better, it may aggravate the oxidative stress of the ischemic tissue.