大鼠局灶性脑缺血再灌注早期非嘌呤非嘧啶核酸内切酶/氧化还原因子-1表达的研究

The expression of APE/Ref-1 at early stage of focal cerebral ischemia/reperfusion in rats

目的 探讨大鼠大脑中动脉阻塞再灌注 (MCAO/R)后 ,DNA修复酶非嘌呤非嘧啶核酸内切酶 /氧化还原因子 1(APE/Ref 1)的表达变化及其意义。方法 采用免疫组织化学方法检测APE/Ref 1在缺血再灌注早期损伤脑组织中的变化。结果 自再灌注 2h起 ,损伤侧APE/Ref 1表达阳性细胞数较相应的假手术对照组和正常组显著下降(P <0 .0 1) ,至 48h各手术组间APE/Ref 1表达并无明显差异 (P >0 .0 5 ) ,72h时损伤区域APE/Ref 1表达较其他手术组减少 (P<0 .0 1) ;2～ 48h ,损伤侧及损伤对侧相应区域部分APE/Ref 1的表达出现于胞质 ,72h时损伤对侧恢复为胞核表达 ,且无细胞减少。结论 局灶性大鼠脑缺血再灌注早期 ,DNA修复酶APE/Ref 1在损伤区域的表达水平降低 ,并出现该蛋白的胞质滞留现象 。

Objective To study the expression of apurinic apyrimidinic endonuclease/redox factor 1(APE/Ref 1) at different time points of reperfusion after middle cerebral artery occlusion(MCAO)for two hours.Methods The level of APE/Ref 1 was measured by immunohistochemical technology.Results From the second hour of reperfusion,the APE/Ref 1 positive cells at damaged side in operation groups were less than those in sham operation and control groups(P<0.01),and by 48 h,there was no difference between the operation groups of different reperfusion time(P>0.05). Compared with other operation groups,the number of positive cells of 72 hour reperfusion group remarkably decreased in damaged area(P<0.01). From 2 to 48 hours,expression of APE/Ref 1 appeared in cytoplasm of corresponding areas at both sides.After 72 hours APE/Ref 1 reappeared in nuclei at undamaged side.Conclusions At early stage of MCAO/reperfusion,DNA repairing enzyme APE/Ref 1 on damaged side decreased remarkably,and the protein was retained in cytoplasm,demonstrating that DNA repairing function was weakened at early stage,which might play an important role in accelerating cell death in damaged regions.