粒细胞集落刺激因子对大鼠脑缺血再灌注损伤脑Caspase-3与细胞色素C表达的影响  

The effect of granulocyte colony-stimulating factor on the expressions of caspase-3 and cytochrome C protein following cerebral ischemia/reperfusion injury in rats

作　　者：张释双[1] 马静萍[1] 

机构地区：[1]山西医科大学第一临床医学院神经内科,030001

出　　处：《中国神经免疫学和神经病学杂志》2011年第4期269-272,共4页Chinese Journal of Neuroimmunology and Neurology

摘　　要：目的探讨粒细胞集落刺激因子(G-CSF)在大鼠脑缺血再灌注损伤中的神经保护作用机制。方法将36只健康成年雄性SD大鼠随机分为假手术组、缺血再灌注组、G-CSF治疗组,每组12只。采用线栓法制作大鼠大脑中动脉缺血再灌注模型,于脑缺血2 h再灌注0 h及24 h给予G-CSF治疗组G-CSF(按体质量50μg/kg)腹部皮下注射,给予假手术组和缺血再灌注组等量生理盐水。采用Longa评分法进行神经功能评分,采用免疫组化法检测各组大鼠脑组织细胞色素C、半胱氨酸蛋白酶-3(Caspase-3)表达水平,应用原位末端转移酶标记(TUNEL)检测神经细胞凋亡情况,TTC染色检测脑梗死体积。结果假手术组大鼠未发现脑梗死病灶,细胞色素C和Caspase-3阳性细胞数及凋亡细胞亦少见。G-CSF治疗组细胞色素C、Caspase-3阳性细胞数及凋亡细胞数均较缺血再灌注组明显减少(P<0.01);缺血再灌注组和G-CSF治疗组均可见大脑中动脉供血区梗死灶,但G-CSF治疗组梗死灶较缺血再灌注组明显缩小(P<0.01),神经功能明显改善。结论 G-CSF对脑缺血再灌注损伤有神经保护作用,其作用机制可能通过阻断线粒体/细胞色素C途径抑制细胞凋亡。Objective To explore the neuroprotective mechanisms of granulocyte colony-stimulating factor （G-CSF） in brain damage following cerebral ischemia/reperfusion in rats. Methods Thirty-six male Sprague-Dawley rats were randomly divided into the sham-operated group, the middle cerebral artery occlusion/ reperfusion group （MCAO/R） and the G-CSF-treatment group, and 12 rats were included in each group. The temporary middle cerebral artery occlusion reperfusion model was made by the suture method. In G-CSF-treatment group, a single dose of 50μg/kg G-CSF was injected subcutaneously at the onset of reperfusion and 24 hours after the reperfusion. The sham-operated group and MCAO/R group received the same volume of saline. The expressions of cytoehrome C （Cyt C） and caspase-3 were detected by immunohisto-chemistry and the apoptosis cells were shown by TUNEL method. The infarction volume was revealed by TTC stain and the neurological function was scored with Longa 5-point scale. Results In the sham-operated group, no infarction was observed, Cyt C （＋）, caspase-3 （＋） cells and apoptotic cells were hardly to be found; However, a lot of Cyt C （＋）, caspase-3 （＋） cells and apoptotic cells were found in the MCAO/R group and the G-CSF-treatment group. Compared with the MCAO/R group, the expressions of Cyt C and caspase-3, and percentage of apoptotic cells decreased significantly in the G-CSF-treatment group （P〈0.01）. The infarction volume and neurological outcome scores of the G-CSF-treatment group were lower than those of the MCAO/R group （P〈0.01） with obviously improved neurological function. Conclusions G-CSF could protect brain from ischemia/reperfusion injury, and this may be achieved by protecting mitochondria function to reduce apoptosis.

关 键 词：粒细胞集落刺激因子 再灌注损伤 细胞凋亡 半胱氨酸内肽酶类 细胞色素C类 

分 类 号：R743.3[医药卫生—神经病学与精神病学]