一氧化氮对大鼠脑缺血再灌注后JNK3、Bad(ser128)和c-Jun磷酸化的影响

Effects of Nitric oxide on the phosphorylation of JNK3,Bad (ser128) and c-Jun following cerebral ischemia-reperfusion in rats

目的探讨一氧化氮对大鼠脑缺血再灌注后JNK3、Bad(ser128)和c-Jun磷酸化的影响。方法90只健康SD(Sprague-Dawley)大鼠随机分为假手术组、缺血再灌注组(对照组)、硝普钠组、硝普钠+阻断剂组(阻断剂组)和溶剂组。以大鼠四动脉结扎脑缺血模型为基础,应用焦油紫染色法检测海马CA1区神经元凋亡,采用免疫印迹和免疫沉淀法检测JNK3、Bad(ser128)和c-Jun的磷酸化。结果硝普钠组脑海马CA1区神经元凋亡显著少于对照组、阻断剂组及溶剂组(P<0.05),对照组、阻断剂组及溶剂组之间差异无显著性(P>0.05);硝普钠组JNK3、Bad(ser128)和c-Jun的磷酸化显著低于对照组、阻断剂组及溶剂组(P<0.05),对照组、阻断剂组及溶剂组之间差异无显著性(P>0.05)。结论一氧化氮供体硝普钠能显著减轻脑缺血再灌注后脑海马CA1区神经元凋亡,明显抑制JNK3、Bad(ser128)和c-Jun的磷酸化水平,对脑缺血再灌注损伤起到保护作用。

[Objective] To investigate the effects of Nitric oxide on the phosphorylation of JNK3, Bad （ser128） and c-Jun following cerebral ischemia-reperfusion in rats. [Methods] 90 Adult male SD （Sprague-Dawley） rats were randomly divided into sham-operated group, iscbemia-reperfusion group （control group）, SNP opener treatment group （SNP group）, SNP＋blocker treatment group （blocker group） and solvent group. Based on the four-vessel occlusion models, neuron apoptosis in CA1 region of hippocampus was detected by cresyl violet staining, the phospho- rylation of JNK3, Bad （ser128） and c-Jun were detected by immunoblotting and immunoprecipitation. [Results] The number of apoptoticneurons in SNP group were significantly less than that of control group, blocker group and solvent group （P 〈0.05）. There were no differences between control group, blocker group and solvent group（P 〉0.05）. The phosphorylafion of JNK3, Bad（ser128） and c-Jun in SNP group was significantly less than that in control group, blocker group and solvent group （P 〈0.05）, there were no differences between control group, blocker group and solvent group （P 〉0.05）. [Conclusion] Nitric oxide donor SNP has a protective effect on neuron in CA1 region of hippocampus following cerebral ischemia-reperfusion by significantly decreasing the phosphorylation of JNK3, Bad （ser128） and c-Jun and neuronal apoptosis.