摘要
目的观察胶质细胞源性神经营养因子(GDNF)与bcl-2基因对大鼠局灶性脑缺血再灌注损伤(CIRI)的影响。方法取健康Wistar大鼠40只,采用Longa改良栓线法制成大脑中动脉闭塞(MCAO)模型,缺血2h后再灌注,随机分4组:对照组、bcl-2组、GDNF组、bcl-2+GDNF组,于再灌注3h后经侧脑室注射GDNF10μl、经颈动脉注射pLXSN-bcl-2质粒10μg,MCAO后3d(n=5),14d(n=5),通过免疫组化染色检测bcl-2蛋白和GDNF的表达情况,TUNEL法检测细胞凋亡情况。结果bcl-2+GDNF组bcl-2蛋白表达与GDNF表达水平均较其他组表达明显增加(P<0.05),bcl-2组、GDNF组较对照组明显增加(P<0.05);脑内细胞凋亡GDNF+bcl-2组较其他组明显减少(P<0.05),bcl-2组、GDNF组较对照组明显减少(P<0.05)。结论bcl-2基因和GDNF可能通过减少神经细胞凋亡,促进bcl-2与GDNF蛋白表达,增强对局灶性缺血脑组织的保护能力,加速中枢神经损伤的修复;bcl-2基因与GDNF协同作用,促使神经细胞在脑内的凋亡进一步减少,从而避免脑缺血再灌注后脑细胞进一步损伤。
Objective To observe the effect of bcl-2 gene and glial cell line-derived neurotrophic growth factor (GDNF)in rats with focal cerebral ischemia reperfusion injury. Methods Middle Cerebral Artery Occlusion(MCAO)models were made by reforming Longa method in 40 healthy Wistar rats,Reperfusion was implemented two hours later.The rats were randomly divided into 4 groups:control group、bcl-2 group、GDNF group and GDNF+bcl-2 group.Three hours after reperfusion,10 μg PlXSN-bcl-2 gene was injected into internal carotid artery, 10 μl GDNF was injected into the lateral cerebral ventricle under stereotaxis,3 or 14 days later,5 rats in each group were sacrificed respectively,GDNF and bcl-2 protein expression were determined through immunohistochemistry,and the distribution of apoptosis neurons was checked out by TUNEL techniques. Results There was significant increase in the expression of bcl-2 protein and the expression of GDNF not only in bcl-2+ GDNF groups compared to other groups(P < 0.05),but also in bcl-2 group and GDNF group compared to control group (P < 0.05);There was significant decrease in the apotosis of nerve cells not only in bcl-2+ GDNF group compared to other groups (P < 0.05),but also in bcl-2 group and GDNF group compared to control group(P < 0.05). Conclusion bcl-2 gene and GDNF maybe protect focal ischemic brain tissue and accelerate repair of central nervous system damage through reduction of neuronal apoptosis of nerve cells in the brain so as to avoid cerebral ischemia reperfusion injury of brain cells.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2009年第12期900-903,共4页
Journal of China Medical University
