SP600125对大鼠脑缺血再灌注神经元的保护作用

目的探讨SP600125-JNK特异性抑制剂对大鼠脑缺血再灌注神经元损伤的保护性作用及其作用机制。方法雄性SD大鼠54只,体重230～250g,随机分成假手术组（SH组）,缺血再灌注组（IR组）和JNK抑制剂SP600125组（SP组）,每组根据再灌注时间分为30min、24h和72h3个亚组,每亚组6只动物。采用4-VO法建立SD大鼠脑缺血模型,三组于缺血前30min侧脑室注射DMSO,DMSO及JNK抑制剂SP600125（溶媒采用DMSO）,容积均为10μl;脑缺血再灌注后30min、24h、72h免疫组织化学方法测定各时间点海马CA1区Bcl-2和Bax蛋白表达阳性细胞数量,TUNEL法检测CA1区凋亡细胞。结果缺血再灌注使海马CA1区Bcl-2和Bax阳性锥体细胞数目表达增加,再灌注24h阳性锥体细胞数目表达至高峰（P〈0.01）,再灌注24～72h可见阳性锥体细胞数目表达减少（P〈0.05）。其中SP组Bcl-2阳性锥体细胞数目显著多于IR组（P〈0.05）,而Bax阳性锥体细胞数目显著小于IR组（P〈0.05）。脑缺血再灌注后海马CA1区神经元存活数目SP组高于IR组（P〈0.01）,凋亡细胞数目低于IR组（P〈0.01）。结论 SP600125对大鼠脑缺血再灌注神经元损伤具有保护作用。

Neuroprotective effect of SP600125 on brain ischemia/reperfusion in rats

Objective To investigate the neuroprotective effect of SP600125 on cerebral ischemia/reperfusion in rats and its possible mechanism.Methods 54 SD rats weighing 230～250g were randomly divided into sham operation group（SH）,ischemia/reperfusion group（IR） and JNK inhibitor SP600125 group（SP）.The rats were given DMSO（SH group）,DMSO（IR group） and SP600125（SP group,the use of DMSO solvent） of 30min before ischemia respectively by intracerebroventricular injection.Each group divided into 3 subgroups according to reperfusion time 30min,24h and 72h（each subgroup of 6 animals）.The establishment of SD rat model of global cerebral ischemia was induced by four-vessel occlusion.The number of survival pyramidal cells bax and Bcl-2 positive pyramidal cells in the CA1 subfield of hippocampus were counted at the time points of 30min,24h and 72h after reperfusion were immunohistochemical methods and TUNEL.Results Immunohistochemistry results showed that after ischemia-reperfusion Hippocampal CA1 area Bcl-2 and Bax positive expression increased the number of pyramidal cells,24h of reperfusion the number of pyramidal cells shows that the expression of positive to the peak（P0.01）.After ischemia/reperfusion 24h to 72h.Positive expression to reduce the number of pyramidal cells（P0.05）.With the IR group,SP group Bcl-2-positive pyramidal cells increased the number（P0.05）.Bax-positive increase in the number of pyramidal cells less（P0.05）.In SP group,the living neurons in hippocampal CA1 region were much more than those in IR group（P0.01）,and the apoptotic neurons were much less than those in IR group（P0.01）.Conclusion SP600125 protects the neurons from apoptosis and death in rat hippocampal CA1 region during whole brain ischemia/reperfusion injury.