垂体腺苷酸环化酶激活肽对大鼠脑缺血再灌注损伤后缺血皮层 p-ERK及c-Fos表达的影响

目的观察大鼠局灶性脑缺血再灌注损伤后活化的胞外信号调节激酶和c-Fos的表达变化及垂体腺苷酸环化酶激活肽(PACAP)对其表达的影响。方法采用大鼠局灶性脑缺血再灌注损伤模型,72只大鼠随机分成假手术组、缺血再灌注对照组、缺血再灌注PACAP治疗组,大脑中动脉阻塞2h分别再灌注2、12、24、48h。再灌注后各时间点进行神经功能学评分后处死大鼠,免疫组织化学法分别检测3组大鼠p-ERK及c-Fos表达水平。结果缺血再灌注不同时间点PACAP组大鼠神经功能学评分较缺血再灌注对照组减低。脑缺血诱导JNK活化,缺血再灌注对照组缺血侧皮层p-ERK 2h达高峰后渐下降;c-Fos分别在2、24h表达高峰。与之相比,PACAP组各时间点p-ERK表达升高,24、48h c-Fos表达下降。结论PACAP对局灶性脑缺血再灌注损伤有保护作用,部分依赖于其上调了磷酸化EPK的表达,并下调了延迟表达的c-Fos基因。

Effects of PACAP on the expression of p-ERK and c-Fos in cortex of rats after ischemia-reperfusion

Objective To observe the expression of activated extracellular signal-regulated kinase(ERK) and c-Fos after focal cerebral ischemia-reperfusion injury in rats and the effects of PACAP.Methods The model of focal cerebral ischemia-reperfusion injury was made by occluding middle cerebral artery(MCA) for 2h and reperfusing for 2,12,24 and 48 hours.72 rats were randomly divided into 3 groups,sham-operated group,ischemia-reperfusion control group and PACAP treatment group.Neurological scoring was done at different times after reperfusion.The rats were killed and immunohistochemical technique was used to examine the expressions of p-ERK and c-Fos in three groups respectively.Results Neurological deficits score showed that the score in PACAP group was lower than that in control group at different time points after reperfusion.The expression of p-ERK reached the peak at 2 h after reperfusion in ischemic cortex,while the higher expression of c-Fos appeared at 2 hours and 24 hours.As compared with ischemia contral group,the expression of p-ERK was significantly discreased at all times in PACAP group,while the level of c-Fos was merely discreased at 24 hours and 48 hours.Conclusion PACAP plays a protective role on focal cerebral ischemia-reperfusion injury in rats.The mechanism partially mediated by up-regulating p-ERK and down-regulating the delayed expression of c-Fos.