摘要
目的 探讨大鼠局灶性脑缺血再灌注后DNA修复蛋白PARP基因表达的时空改变及其与凋亡的关系。方法 采用大鼠大脑中动脉阻塞再灌注模型 (MCAO R) ,运用原位杂交技术观察缺血再灌注PARPmRNA的时空分布 ,结合TUNEL技术观察其与凋亡的关系。结果 脑缺血 30min再灌注 1hPARPmRNA表达增加 ,随缺血或再灌注时间的延长表达逐渐增强 (P <0 0 5 ) ,与凋亡的时间变化规律相似 ,但范围大于并涵盖凋亡的范围 ,凋亡分布区外侧的缺血区表达也明显增加。结论 脑缺血 /再灌注损伤可诱导神经细胞DNA修复蛋白PARP基因的转录增强 ,PARP可能参与脑缺血损伤后的DNA修复。
Objective In this study,we explored the gene expression of poly(ADP-ribose)Polymerase(PARP),and the role of PARP in apoptosis and DNA repair following transient focal cerebral ischemia in rats.Methods Adult Wistar rats were respectively subjected to 30 min and 2 h of transient focal cerebral ischemia induced by intraluminal blockade of the left middle cerebral artery, followed by 1～48 h of reperfusion. PARP mRNA level was measured by in situ hybridization technique. Apoptosis was evaluated by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-flourescein nick end-labeling (TUNEL) assay in adjacent sections.Results PARP mRNA increased after 30 min of occlusion with 1 h of reperfusion. The expression was ischemia-and reperfusion-time dependent. Apoptosis was observed in the inner boundary zone of infarction, with a temporal profile similar to that of PARP mRNA expression. However, in the outer ischemic area with few apoptotic cells, the expression of PARP mRNA was also increased at all time points studied.Conclusions Our findings provide evidence that PARP gene expression is up regulated after transient focal cerebral ischemia.The altered PARP gene expression plays a role for PARP in repairing DNA after brain ischemic injury.
出处
《中华急诊医学杂志》
CAS
CSCD
2004年第1期21-23,i001,共4页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金重点项目 ( 3 970 170 )
国家自然科学基金资助项目 ( 3 9770 810 )
国家自然科学基金项目( 3 0 0 70 82 5 )
关键词
DNA修复蛋白
PARP
大鼠
脑缺血
再灌注损伤
基因表达
Poly(ADP-ribose) polymerase
Gene expression
DNA damage
DNA repair
Cerebral ischemia/reperfusion
