c-fos在肢体缺血预处理抗脑缺血再灌注损伤中的作用

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

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。

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 immunohistochemieal 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 gyms 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.