大鼠脑缺血再灌注后胰岛素样生长因子-1的表达及意义  

The Expression and Significance of Insulin-like Growth Factor-1 in Rats with Focal Cerebral Ischemia-reperfusion

作　　者：刘薇[1] 张祥建[1] 胡明[1] 崔海瑛[1] 狄楠[1] 

机构地区：[1]河北医科大学第二医院神经内科,河北省石家庄市050000

出　　处：《中国卒中杂志》2008年第8期581-586,共6页Chinese Journal of Stroke

摘　　要：目的观察胰岛素样生长因子-1(IGF-1)在大鼠脑缺血再灌注后在缺血不同部位的表达及组织病理学改变,探讨其对神经元的保护作用。方法72只清洁级、成年健康雄性SD大鼠随机等分为假手术对照(sham)组和脑缺血再灌注(CIR)组,CIR组缺血3h后,按再灌注时间的长短不同分为0、6、24、48、72h和7d6个亚组,每亚组均为6只大鼠。于各相应时间点以Longa法、Berderson法和平衡木法分别进行行为学评分后处死动物,制做脑组织病理切片,苏木精-伊红染色后观察组织病理学改变,采用免疫组织化学方法测定IGF-1的动态表达变化。结果(1)大鼠在大脑中动脉阻断后手术对侧肢体存在不同程度瘫痪,24h后行为学评分结果逐渐趋于稳定,根据观察大鼠病变对侧肢体出现不同程度的瘫痪,其功能异常程度与病变严重程度一致;(2)除假手术对照(sham)组外,其余各组在脑梗死后6h局部可见少量散在炎性细胞浸润,梗死后48h炎性细胞浸润明显增多,并持续到7d;(3)IGF-1在sham组神经元中呈弱阳性表达(灰度值127±6);CIR组各缺血时段IGF-1表达分别为147±5(0h)、153±6(6h)、170±7(24h)、169±5(48h)、150±6(72h)和147±5(7d)。其中,缺血3h及缺血3h再灌注6h组中心区、半影区阳性细胞数均增多,表达增强;随再灌注时间延长,中心区表达接近正常水平,半影区阳性细胞数增多,表达呈持续升高趋势,再灌注24h和48h达高峰,72h表达有所下降,但仍表达高水平。结论高表达的IGF-1参与了脑缺血再灌注后内源性神经保护过程,IGF-1在缺血半影区与中心区的演变病理生理中起重要作用,说明IGF-1对缺血半影区的保护作用。Objective To observe the expression of insulin-like growth factor-1(IGF-1) and the change of histopathology in the ischemic region of rats with focal cerebral ischemia-reperfusion,so as to explore the neuron protection of IGF-1.Methods All the rats were divided into sham group and cerebral ischemia-reperfusion(CIR) group randomly,36 rats for each group.After ischemia for 3h,according to the time of reperfusion(0h,6h,24h,48h,72h and 7d),the CIR group and sham group were both divided into 6 subgroups and every subgroup was 6 rats.The neurological deficit score(NDS) was assessed with 3 different methods,and histopathology changes were observed with hematoxylin and eosin(HE) staining.We observed the expression of IGF-1 by immunohistochemistry.Results ①The ethology score increased after the operation and at 24 to 72h after reperfusion the scores of CIR group were more than those of sham group.At 7d after reperfusion the ethology score was almost normal in CIR group.②In the CIR group,we found the inflammatory cell infiltration in the infarction regions with the peak at 48h,and continued to 7d.③The expression of IGF-1 was very low in normal tissues,while increased mainly in infarction regions after cerebral ischemia.In CIR group the expressions of IGF-1 protein were 147±5,153±6,170±7,169±5,150±7,147±5 at the time of reperfusion(0h,6h,24h,48h,72h and 7d) respectively.At 0h and 6h after reperfusion the positive cells expressed IGF-1 in central and penumbra region increased and with the time prolonged,the expressions were normal in the central region but still increased in penumbra region,and reached the peak at 24 h and 48h after reperfusion.At 72h after reperfusion the expression of IGF-1 protein decreased but was also higher than that of sham group.Conclusion Enhanced expression of endogenous IGF-1 has protective effects on focal cerebral ischemia reperfusion injury.

关 键 词：脑缺血 再灌注损伤 胰岛素样生长因子-1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]