一氧化氮参与肢体缺血后处理对全脑缺血-再灌注损伤的保护作用

Neuroprotective role of nitric oxide in participating in limb ischemic postcoditioning against global cerebral ischemia/reperfusion injury

目的探讨NO在肢体缺血后处理(RIPoC)减少大鼠全脑缺血-再灌注(IR)损伤过程中的作用。方法用四动脉阻断法建立全脑IR模型。选择成年雄性SD大鼠120只,200～250g,随机分为四组:Sham组,IR组,IR+RIPoC组,L-NAME+IR+RIPoC组。IR后7d取脑组织行Nissl染色,观察海马CA1区存活神经细胞的数目;48h取脑组织行TUNEL检测,观察海马CA1区神经细胞的凋亡。检测IR后1.5、12、24、48h血清以及海马CA1区的NO含量及NOS活性。结果与Sham组比较,IR组7d的CA1区神经细胞数目明显减少,48h的TUNEL阳性细胞数量明显增加(P<0.01)。与IR组比较,IR+RIPoC组7d的海马CA1区神经细胞数目明显增加(P<0.01),48h的TUNEL阳性细胞数量明显减少(P<0.01),IR后血清及CA1区的NO含量和NOS活性明显增加(P<0.05或P<0.01)。与IR+RIPoC组比较,L-NAME+IR+RIPoC组7dCA1区神经细胞数目明显减少,48h的TUNEL阳性细胞数量明显增加,IR后血清及CA1区的NO含量明显减少,血清NOS活性明显降低(P<0.05)。结论 RIPoC对全脑IR后损伤的神经细胞有保护作用,其机制与RIPoC调节血清及脑内的NO及NOS有关。

Objective To investigate the role of nitric oxide （NO） in the neuroprotective effects on remote ischemic postconditioning （RIPoC） against global cerebral ischemia/reperfusion （IR） injury, Methods One hundred and twenty male Sprague-Dawley rats weighing 200-250 g were randomly divided into four groups, group Sham, group IR, group IR＋RIPoC and group L-NAME＋IR＋RIPoC. The number of neurocyte in hippocampal CA1 region were counted by Nissl staining at 7 d after IR, and neuronal apoptosis were observed by TUNEL detection at 48 h. The content of NO and activity of NOS in hippocampal CA1 region were detected at 1.5, 12, 24, 48 h after IR. Results Compared with group Sham, the number ofneurocyte in CA1 at 7 d were decreased, and the TUNEL positive cells at 48 h were increased significantly in group IR（P〈0.01）. Compared with group IR, neurocyte count of group IR＋RIPoC in CA1 at 7 d were higher （P〈 0.01）, and the TUNEL positive cells count at 48 h were fewer（P〈0.01）. The content of NO and activity of NOS in serum and CA1 of group IR＋RIPoC were higher than in group IR（P〈0. 05 or P〈0. 01）. Compared with group IR＋RIPoC, the number of neurocyte in CA1 at 7 d and the content oF NO in both serum and CA1 were obviously decreased, while the TUNEL positive cells count at 48 h were increased（P〈 0. 05）. Conclusion RIPoC protects brain against global cerebral IR injury and NO is highly involved in the neuroprotection of RIPoC in 4-VO rats.