老年脑缺血/再灌注大鼠炎症级联反应变化及其意义

目的观察老年脑缺血／再灌注（I／R）大鼠肿瘤坏死因子-α（TNF—α）、细胞间黏附分子-1（ICAM-1）和血管内皮黏附分子-1（VCAM-1）及ICAMmRNA表达的变化，探讨老年脑I／R损伤的病理生理机制。方法36只青年（5～6月龄）SD大鼠和36只老年（20～21月龄）SD大鼠，均为雄性，采用随机方法将其分别分为青年假手术组、老年假手术组、青年模型组和老年模型组。两个模型组又各随机分为缺血3h（13h）和I／R1、3、6、12d时间点，每个时间点6只大鼠。采用大脑中动脉栓塞（MCAO）方法复制脑I／R损伤动物模型，观察各组大鼠各时间点神经功能障碍评分，脑组织含水量，脑组织病理学，TNF—α、VCAM-1、ICAM-1及ICAMmRNA表达的变化。结果老年假手术组TNF—α表达高于青年假手术组；青年模型组和老年模型组脑组织含水量（I／R1～6d）、神经功能障碍评分（I3h及I／R1～12d）、TNF—α（I3h及I／R1～6d）、VCAM-1（I3h及I／R1～12d）、ICAM-1（I3h及I／R1～6d）及ICAM-1mRNA（I3h及I／R1～12d）表达均高于同龄假手术组；老年模型组神经功能障碍评分（I3h、I／R6d）、TNF—α（I／R1d、3d）、VcAM-1（I／R 3d、6d）、ICAM-1（I3h、I／R1d）及IcAM-1 mRNA（I／R1～6d）表达均高于青年模型组。结论脑I／R损伤与TNF—α、VCAM-1、ICAM-1表达增加有关，老年脑I／R损伤严重可能为随着增龄TNF—α和黏附分子表达增强所致。

Changes in inflammatory cascade response and its implication during cerebral ischemia/reperfusion in aged rats

OBJECTIVE: To investigate the changes in expression of tumor necrosis factor-alpha(TNF-alpha), vascular cellular adhesive molecule-1 (VCAM-1), intercellular adhesion molecular-1 (ICAM-1) and its mRNA expression, and the pathogenetic mechanism of cerebral ischemia/reperfusion(I/R) in elderly. METHODS: Thirty six male young SD rats (5-6 months old) and 36 male aged SD rats (20-21 months old) were randomly divided into young sham operated group, young model group, aged sham operated group and aged model group, respectively. The two model groups were randomly divided into ischemia 3 hours (I 3 h), I/R 1, 3, 6, 12 days groups. There were 6 rats in each group. Focal cerebral I/R model was replicated with middle cerebral artery occlusion (MCAO). The changes of the nervous dysfunction score, the water content of cerebral constitution and the expression of TNF-alpha, VCAM-1, ICAM-1 and ICAM-1 mRNA were observed at each time point. RESULTS: The expression of TNF-alpha in the aged sham operated group were higher than that of the young sham operated group. The nervous dysfunction score (I 3 h and I/R 1-12 d), the water content of cerebral constitution (I/R 1-6 d), the expression of TNF-alpha (I 3 h and I/R 1-6 d), VCAM-1 (I 3 h and I/R 1 d), ICAM-1 (I 3 h and I/R 1-6 d) and ICAM-1 mRNA (I 3 h and I/R 1-12 d) in young model group and aged model group were higher than those of the young sham operated group and the aged sham operated group respectively. The nervous dysfunction score (I 3 h, I/R 6 d), the expression of TNF-alpha (I/R 1, 3 d), VCAM-1 (I/R 3, 6 d), ICAM-1 (I 3 h, I/R 1 d) and ICAM-1 mRNA (I/R 1-6 d) in aged model group were higher than that of young model group. CONCLUSION: The cerebral I/R injury is correlated with the up regulation of TNF-alpha, VCAM-1,ICAM-1 and its mRNA expression. The cerebral I/R injury of aged rats is more serious than that of young rats which might be associated with up regulation of TNF-alpha, adhesion molecules expression with aging.