摘要
目的:观察髓鞘相关生长抑制因子Nogo-A及胰岛素样神经生长因子受体在脑缺血再灌注损伤大鼠脑组织区域的表达特点。方法:实验于2005-08/2006-04在青岛大学医学院附属医院脑血管病研究所进行。将80只成年健康雄性Wistar大鼠,采用双盲法随机分为正常对照组8只、假手术组8只、缺血再灌注组64只,缺血再灌注组分为2h、6h、12h、24h、48h、3d、7d、14d8个时间点,每个时间点8只,其中4只用于Nogo-A检测,另外4只用于胰岛素样神经生长因子受体的检测。应用线栓法制备大鼠大脑中动脉缺血再灌注动物模型,假手术组不插尼龙线,正常对照组不做任何处理。采用免疫组织化学方法检测脑组织Nogo-A与胰岛素样神经生长因子受体在神经细胞中的表达。结果:80只大鼠均进入结果分析。①Nogo-A蛋白表达:正常对照组及假手术组皮质、海马及纹状体区凋亡细胞呈基础表达。缺血再灌注6～12h皮质区及纹状体区Nogo-A表达达高峰,海马区表达明显增加。缺血再灌注24h均开始下降。缺血再灌注48h～3d皮质区及纹状体区均二次达高峰,海马区表达恒定。缺血再灌注7～14d均降至基础水平。缺血再灌注各组Nogo-A蛋白表达均高于正常对照组及假手术组(P<0.05)。②胰岛素样神经生长因子受体蛋白表达:正常对照组及假手术组在皮质、海马及纹状体区阳性细胞呈基础表达。缺血再灌注24h达高峰,48h恒定表达,3～14d仍维持高值表达。缺血再灌注各组胰岛素样神经生长因子受体蛋白表达均高于正常对照组及假手术组(P<0.05)。结论:脑缺血再灌注损伤后,大鼠脑海马、皮质、纹状体等区域Nogo-A与胰岛素样神经生长因子受体表达均增加。胰岛素样生长因子受体表达增加与损伤程度呈正相关,脑轻度损伤时胰岛素样生长因子受体表达仅限于大脑皮质区,重度损伤时弥漫整个海马及纹状体区。
AIM： To explore the characterisitics of the expressions of myelin-associated inhibitor factor Nogo-A and insulin-like nerve growth factor Ⅰ receptor （IGF- Ⅰ R） in rat brain tissues after cerebral ischemialreperfusion injury.
METHODS： The experiment was carried out in the Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College between August 2005 and April 2006. With double blind method, eighty healthy adult male Wister rats were randomly divided into control group （n =8）, sham-operetion group （n =8） and ischemia/reperfusion group （IR, n =64）. The IR group was subdivided into 2, 6, 12, 24, 48 hours and 3, 7, 14 days groups with 8 rats at each time point, in which 4 animals were used for Nogo-A detection, and the others for IGF- Ⅰ R test. The models of cerebral ischemia/reperfusion were established by intraluminal middle cerebral artery occlusion with a nylon monofilament suture; the sham-operation group did not insert the nylon suture, and the control group was not given any treatment. The expressions of Nogo-A protein and IGF- Ⅰ R protein in neurons were detected with immunohistochemical technique.
RESULTS： Eighty rats entered the result analysis. ①Expression of Nogo-A protein： The expression was found in the apoptotic nerve cells in cortical area, hippocampus, and striatal area of the normal control group and sham-operation group. The expression of Nogo-A appeared peak in the cortical area and striatal area after reperfusion for 6 to 12 hours, which was significantly increased in hippocampus neurons. It began to decrease after reperfusion for 24 hours. The second expression peak appeared from 48 hours to 3 days in cortical area and striatal area, and the expression in the hippocampus appeared constant. The expression reached the basic level from 7 days to 14 days. The Nogo-A protein expressions of each IR group were higher than the normal control group and sham-operation （P 〈 0.05）. ②Expression of IGF- Ⅰ R： The expression was found in the positive nerve cells in hippocampus, cortical area and striatal area of the normal control group and sham-operation group. It reached peak after 24 hours reperfusion, and was kept stably at 48 hours. From 3 days to 14 days, it still kept high expression. The IGF- Ⅰ R expressions of each IR group were higher than the normal control group and sham-operation （P 〈 0.05）.
CONCLUSION： Nogo-A and IGF- Ⅰ R are expressed in the cortical area, hippocampus, and striatal area after cerebral ischemia/reperfusion injury. The increase in IGF- Ⅰ R expression is positively related with injury degree; the expressions are only found in the cortical area under mild injury, which are found in the hippocampus and striatal area under severe injury.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第14期2633-2636,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
青岛市科技局基金资助项目(05-1-NS-73)~~
