【作者】 余锋；

【导师】 任明山； 李光武；

【作者基本信息】 安徽医科大学 ， 神经病学， 2005， 硕士

【摘要】 目的:探讨局灶性脑缺血再灌注损伤的动态病变特点及明胶酶、TIMP-1、GFAP、PCNA的表达与损伤机制的关系。方法:建立大鼠MCAO/R模型,采用HE染色、Tunel染色并结合脑含水量(干湿重法)测定以观察大鼠局灶性脑缺血2h再灌注后3h、24h、48h、72h、5d、7d不同时间点脑组织的病理变化;并应用SP免疫组织化学方法检测各相应时间点大鼠缺血区大脑组织中的MMP-2、MMP-9、TIMP-1、GFAP、PCNA的蛋白表达。 结果:1) 较假手术对照组相比,局灶性脑缺血再灌注后3h至7d大鼠缺血区大脑组织均有明显病理损伤。水肿出现在再灌注全程中,但呈现两个明显的高峰,分别是再灌注后24h点及72h点,其中前者尚伴片状出血,表明再灌注后24h BBB的损害最严重;缺血中心区的损伤以坏死为主;边缘区的损伤以细胞凋亡为主;炎细胞的浸润从再灌注后24h出现并逐渐加剧;损伤的修复从再灌注后72h开始;但细胞凋亡尤其是缺血边缘区的凋亡持续性存在,不随修复的进行而减轻;细胞凋亡与脑水肿间存在正相关性。 2) 缺血再灌注各组大鼠缺血区大脑组织的MMP-2、MMP-9、TIMP-1表达均较假手术对照组明显升高,有显著性差异,P<0.05;再灌注各组的MMP-2、MMP-9表达及MMP-9/TIMP-1比值存在时空改变且分别与脑水肿、细胞凋亡有正相关性,P<0.01,相关度R值均在0.5以上,其中24h的首次脑水肿高峰与MMP-2表达峰值点及MMP-9/TIMP-1表达比值的峰值点重叠。 3) 再灌注后早期缺血中心区大脑组织中,星形胶质细胞及微血管内皮细胞的PCNA表达先于神经元的PCNA表达,表明神经元损伤发生在胶质细胞损害及脑微环境改变之后;缺血边缘区PCNA、GFAP二者的表达均从72h点明显升高并伴有细胞的增生,与再灌注后第二次脑水肿高峰重叠。更多还原

【Abstract】 Purpose To investigate the development pathological changes of reperfusion injury and its correlation to the expressions of gelatinase, TIMP-1, GFAP and PCNA in cerebral tissues of rat after focal cerebral ischemia Methods 2 hours right intraluminal middle cerebral artery occlusion with 3h-7dreperfusion were induced in 36 SD rats, accompanying with sham operation contral in 7 rats . The development pathological changes of specimens of the brain after3h-7d reperfusion were observed by HE and Tunel stained,the expressions of gelatinase, TIMP-K GFAP and PCNA in cerebral tissues of rats were detected by immunohistochemistry method after focal cerebral ischemia with different reperfusion period.Results there was significant difference in the lesion of cerebral tissue between the groups of local cerebral ischemia with reperfusion and sham operartion groups in rats, P<0.01; vasogenic edema can be observed in the course of reperfusion, peaked at 24h, 72 h respectively ,and at 24h accompanied with focus cerebral hemorrhage.In the core zone of ischemia cerebral tissue, necrosis cells can be observed easily and from 24h to 7d accompanied with inflammation cells infiltration; the hyperplasia of astrocyte and repairment of cerebral tissue began at 72 h after reperfusion ,but apoptosis cells could be observed all the time especially in perilesional (penumbra).There was positive relevant between apoptosis cells and cerebral edema, there were更多还原