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目的 观察肾性高血压大鼠局灶脑缺血再灌注后DNA修复蛋白X线修复交叉互补组 1(XRCC1)蛋白的表达及与DNA片段化损伤的关系。方法 采用双肾双夹法建立肾性高血压大鼠模型 ,在此基础上采用线栓法制作大脑中动脉闭塞模型 ,采用免疫组织化学方法观察假手术组和缺血再灌注后 3h、6h、12h、2 4hXRCC1蛋白表达 ,采用TUNEL方法检测DNA片段化损伤。结果 免疫组织化学染色显示 ,假手术组大脑皮质和海马区出现大量XRCC1表达的阳性细胞 ,再灌注 3h缺血区皮质和海马CA1区XRCC1表达阳性细胞减少 ,即缺血区皮质和海马CA1区XRCC1灰度值升高 ,并一直持续到缺血再灌注 2 4h。缺血再灌注后 3h、6h、12h和 2 4h与假手术组相比差异有显著意义 (P <0 0 5 )。TUNEL染色显示 ,假手术组大脑皮质和海马CA1区未见阳性细胞 ,再灌注 2 4h缺血区皮质和海马CA1区可见较多阳性细胞。结论 脑缺血再灌注后XRCC1蛋白免疫活性下降和DNA修复机制的失败与DNA的片段化损伤及凋亡的发生有关。
Objective To investigate the expression of XRCC1 protein and its relationship with DNA fragmentation after focal cerebral ischemia / reperfusion in renovascular hypertensive rats. Methods The rat model of renal hypertension was established by double-kidney double-clamp method. The middle cerebral artery occlusion model was made by the method of thread-plug method. The changes of apoptosis in the sham-operation group and 3h, 6h after ischemia-reperfusion were observed by immunohistochemistry. 12h, 24hXRCC1 protein expression, using TUNEL method to detect DNA fragmentation damage. Results Immunohistochemical staining showed that a large number of XRCC1 positive cells appeared in the cerebral cortex and hippocampus of sham operation group. The expression of XRCC1 positive cells decreased in cortex and hippocampal CA1 region 3h after reperfusion, Gray value increased, and continued until ischemia and reperfusion 24h. There was significant difference between sham group and 3h, 6h, 12h and 24h after ischemia / reperfusion (P <0.05). TUNEL staining showed that there was no positive cells in cerebral cortex and hippocampus CA1 area in sham-operation group, more positive cells were seen in cortex and hippocampus CA1 area of 24 h after reperfusion. Conclusion The decrease of XRCC1 protein immunoreactivity and the failure mechanism of DNA repair after focal cerebral ischemia / reperfusion are related to the fragmentation of DNA and the occurrence of apoptosis.