大鼠局灶性脑缺血再灌注损伤动态病变及其与MMP-2表达关系

目的探讨大鼠局灶性脑缺血再灌注损伤的病变规律及MMP-2在损伤机制中的作用。方法建立大鼠大脑中动脉缺血再灌注模型,分别采用HE、TUNEL染色法观察缺血2 h再灌注3 h-7 d脑组织的动态病理变化及免疫组化法检测MMP-2的蛋白表达。结果假手术组大鼠脑组织形态结构正常;与之相比,缺血再灌注3 h-7 d组脑组织均有明显病变且差异有显著性(P<0.01);缺血中心区再灌注后3 h以变性损伤为主,24 h-7 d以坏死及继发炎症为主;边缘区一直以持续进行性凋亡为主;水肿贯穿病变全程,分别于再灌注后24 h、72 h两次出现高峰,其中24 h尚伴灶片状出血。缺血再灌注组大鼠大脑组织的MMP-2表达显著高于假手术对照组,P<0.05;MMP-2表达存在时空改变且与脑水肿、细胞凋亡有正相关性,P<0.01,相关度R值在0.5以上,其中24 h的首次脑水肿高峰与MMP-2表达峰值点重叠。结论再灌注后24 h、72 h的两次水肿高峰及迟发、持续性细胞凋亡是再灌注损伤两个最重要的方面,MMP -2表达参与了其机制。

A study on pathological changes of reperfusion injury in cerebral tissues of rat after focal cerebral schemia and its correlation to the expression of MMP - 2

Objective To investigate the pathological changes of reperfusion injury in cerebral tissues of rat after focal cerebral ischemia and its correlation to the expression of MMP - 2. Methods 2 hours right intraluminal middle cerebral artery occlusion with 3 h - 7 d reperfusion were induced in 36 rats, accompanying with sham operation in 7 rats. The pathological chan ges of specimens of the brain after 3 h - 7 d reperfusion were observed by HE and TUNEL stained. the expression of MMP - 2 in cerebral tissues of rats were detected by immunohistochemistry method. Results While necrotic cells were predominantly focused in the core of the infarct and increased profressively by 24 h after reperfusion,TUNEL - positive cells were preferentially located in the boundary zone of the infarctoin and progressively increased up to 7 d;vasogenic edema can be observed and peaked at both 24 h and 72 h after reperfusion. there was significant difference in the expression of MMP - 2 of cerebral tissues between the groups of local cerebral ischemia with reperfusion and sham operartion groups in rats, P < 0.05. The time - and space - depend ent expression of MMP - 2 could be observed. There was positive relevant between the expressions of MMP -2. and cerebral ede ma. Conclusion Both vasogenic edema and delayed apoptosis in perilesional (penumbra) are significant pathological changes in transient focal cerebral ischemia/reperfusion,and its mechanisms was relevant to the expression of MMP -2.