c-fos在肢体缺血预处理抗脑缺血再灌注损伤中的作用

目的探讨c-fos在肢体缺血预处理(LIP)抗脑缺血再灌注损伤中的作用。方法将54只凝闭椎动脉大鼠随机分为假手术组、脑缺血组和LIP+脑缺血组。依据脑缺血后再灌注时间不同,将脑缺血组和LIP+脑缺血组进一步分为16、、247、2 h组,每组大鼠6只。采用免疫组织化学方法检测海马c-fos蛋白的变化。结果假手术组海马各区神经元中未见明显的c-fos蛋白表达阳性产物。脑缺血组海马CA1区再灌注后各个时间点均未见明显的c-fos阳性表达,而海马CA3区再灌注6 h时锥体细胞和齿状回颗粒细胞核中出现大量c-fos蛋白阳性表达产物,再灌注24h时,c-fos的表达开始减弱,72 h时消失。在LIP+脑缺血组,再灌注1 h海马CA1区出现少量c-fos的弱阳性表达;再灌注6 h时,CA1区c-fos表达明显增强,阳性细胞数、阳性细胞总面积和平均吸光度均较假手术组显著升高(P<0.01);再灌注24 h时,CA1区c-fos表达趋于减少;至再灌注72 h时,CA1区c-fos表达恢复至假手术组水平(P>0.05)。结论LIP诱导CA1区c-fos的表达上调可能参与LIP抗脑缺血再灌注损伤作用。

Role of c-fos in protective effect of limb ischemic preconditioning against injuries induced by cerebral ischemia/reperfusion in rats

Objective To investigate the role of c-fos in the protective effect of limb ischemic preconditioning(LIP) against cerebral ischemia-reperfusion injuries.Methods Fifty-four Wistar rats with vertebral arteries permanently occluded were divided into sham operation group,cerebral ischemic group and LIP cerebral ischemic group.Cerebral ischemic group and LIP cerebral ischemic group were further divided into 1,6,24 and 72 h groups according to the time of reperfusion after cerebral ischemia respectively.Changes in the expression of c-fos in the hippocampus were observed using immunohistochemical method.Results There was no obvious c-fos positive expression in every subfield of hippocampus in sham operation group.In cerebral ischemic group,c-fos expression was found in the CA3 subfield and dentate gyrus rather than the CA1 subfield,especially at 6 h after cerebral ischemia,and this expression began to be diminished at 24 h and disappeared at 72 h after cerebral ischemia.In LIP cerebral ischemic group,some weak immunoparticles were found in the hippocampus CA1 at 1 h after cerebral ischemia.The expression of c-fos was obviously enhanced at 6 h,the number and total area of positive cells and optical density were significantly higher compared with sham operation and cerebral ischemia 6 h groups(P<(0.01).) The expression of c-fos tended to decrease at 24 h,and recovered to level of sham operation group level at 72 h.Conclusion The protection conferred by LIP against cerebral ischemia/reperfusion injuries may be associated with the increased expression of c-fos in the hippocampus CA1 induced by LIP.