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目的探讨酸后处理,即在再灌早期给予一段短时间的酸化处理,是否对脑缺血再灌注损伤具有保护作用。方法本实验采用小鼠大脑中动脉栓塞(MCAO)模型和大鼠皮质原代神经元氧糖剥夺(OGD)模型。在再灌早期不同时间点吸入含有20%CO2的混合气体(其余气体为21%O2,59%N2)5 min以降低脑内pH值或利用经20%CO2预孵育的酸化培养液对培养的神经元进行酸处理15 min。结果与MCAO手术对照组相比,再灌5 min和50 min后给予酸后处理均能明显减少再灌24 h后的脑梗死体积并降低神经症状评分,但在再灌100 min后给予酸后处理没有显著神经保护作用。相似地,在神经元OGD模型中,再灌后立即或15 min后给予酸后处理可显著提高再灌24 h的细胞存活率。进一步发现,酸后处理可显著抑制神经元OGD再灌注引起的细胞凋亡及胱天蛋白酶3表达增加。同时,与单纯MCAO组相比,给予酸后处理的小鼠缺血周边区的胱天蛋白酶3表达也明显减少。结论以上结果提示,酸后处理对脑缺血再灌注损伤有明显的保护作用,同时,这种保护作用具有较宽的时间窗。酸后处理作为一种新的内源性保护策略对于治疗缺血性脑损伤具有潜在的临床应用价值。
OBJECTIVE: To investigate whether acid treatment, a short period of acidification in the early stage of reperfusion, has a protective effect on cerebral ischemia-reperfusion injury. Methods The experimental middle cerebral artery occlusion (MCAO) model and the rat primary cortical oxygen glucose deprivation (OGD) model were used in this study. In the early reperfusion different time points inhalation of 20% CO2 mixed gas (remaining gas of 21% O2, 59% N2) 5 min to reduce intracerebral pH or pre-incubated with 20% CO2 acidified culture medium Neurons were acid-treated for 15 min. Results Compared with MCAO surgery group, acid reflux treatment at 5 min and 50 min after reperfusion could significantly reduce the volume of cerebral infarction and reduce the neurological symptom scores 24 h after reperfusion, but after acid reflux for 100 min No significant neuroprotective effect was observed with the treatment. Similarly, administration of acid in the neuronal OGD model immediately after reperfusion or after 15 min significantly increased cell viability at 24 h after reperfusion. It was further found that acid post-treatment significantly inhibited apoptosis and increased caspase-3 expression induced by OGD reperfusion in neurons. At the same time, the expression of caspase 3 in ischemic peripheral zone of mice given acid treatment was also significantly reduced compared with MCAO alone group. Conclusion The above results suggest that acid post-treatment has a significant protective effect on cerebral ischemia-reperfusion injury. At the same time, this protective effect has a wide time window. As a new endogenous protective strategy, acid post-treatment has potential clinical value for the treatment of ischemic brain injury.