杨渊，张苏明，方思羽，张旻，江红，许康，常履华.脑缺血再灌注大鼠神经细胞DNA损伤与凋亡的时空关系分析[J].中华物理医学与康复杂志,2004,(12):
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| 脑缺血再灌注大鼠神经细胞DNA损伤与凋亡的时空关系分析 |
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| DOI： |
| 中文关键词: DNA损伤 P53 细胞凋亡 脑缺血再灌注 |
| 英文关键词: Apoptosis Cerebral ischemia/reperfusion DNA damage P53 |
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| 中文摘要: |
| 目的探讨局灶性脑缺血再灌注大鼠神经细胞DNA损伤与凋亡的时空分布演变过程及两者间的联系。 方法共选取72只成年Wistar大鼠，将其随机分为正常组、假手术组、缺血30 min组及缺血2 h组；后2组大鼠又根据再灌注时间（再灌注1，6，12，24及48 h）不同，各细分为5个亚组。制作大鼠大脑中动脉阻塞再灌注模型（MCAO-R），应用免疫组化法观察脑缺血组织在不同缺血再灌注时间下，其P53表达在空间及程度上的改变，并结合TUNEL技术观察P53表达与细胞凋亡的时空关系。 结果脑缺血再灌注可诱导细胞凋亡及P53蛋白表达增强，并随着缺血或再灌注时间的延长，凋亡细胞数量与P53表达均逐渐增加，但P53蛋白的表达始终早于凋亡细胞的出现，且P53阳性细胞数量始终多于凋亡细胞数量（P<0.05），其分布范围也较凋亡细胞更广。 结论神经细胞缺血可引起DNA损伤，DNA损伤后可诱导DNA修复，如修复失败则启动细胞凋亡程序。 |
| 英文摘要: |
| Objective To investigate the spatiotemporal relationship between the magnitude and extent of cells undergoing DNA damage and apoptosis as a function of duration of reversible middle cerebral artery occlusion in the rat. MethodsA total of 72 adult Wistar rats were recruited and divided into four groups: a normal two groups were subject to transient focal cerebral ischemia induced by intraluminal blockade of the left middle cerebral artery. After different periods of ischemia/reperfusion(1, 6, 12, 24 and 48 h), the number and anatomic distribution of P53 protein were detected by immunohistochemistry technique, and were compared with apoptotic cells examined with the technique of a terminal deoxynucleotidyltranferase (TdT)-mediated dUTP-flourescein nick end-labeling (TUNEL) assay in adjacent sections. ResultsThe dynamic progression of P53 protein expression was approximately consistent with that of apoptosis. Whereas the amounts of P53 immunoreactive cells were significantly higher, the presence was earlier and the distribution was more extended, as compared with those of the apoptotic cells（P<0.05）. ConclusionOur data suggest that DNA damage is an early event after neuronal ischemia and may trigger DNA repair processes, and that the failure of repair of DNA damage may trigger apoptosis. |
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