重组人粒细胞集落刺激因子对大鼠脑缺血再灌注损伤后p-JAK2及p-STAT3信号通路的影响  

The effect of recombinant human granulocyte colony-stimulating factor on the expressions of p-JAK2 and p-STAT3 signal transduction pathways following cerebral ischemia/reperfusion injury in rats

作　　者：徐海发[1] 蒋晶晶[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》2014年第4期273-277,共5页Chinese Journal of Neuroimmunology and Neurology

摘　　要：目的观察SD大鼠大脑中动脉缺血再灌注损伤模型在给予重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,rhG-CSF)后脑组织磷酸化酪氨酸激酶-2(p-JAK2)、磷酸化信号转导子和转录活化子-3(p-STAT3)蛋白表达及细胞凋亡的情况,探讨rhG-CSF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、脑缺血再灌注组、rhG-CSF治疗组(治疗组),每组12只。采用Longa线栓法制作大脑中动脉闭塞再灌注模型(MCAO/R),治疗组大鼠于脑缺血2h后再灌注的即刻及24h分别给予rhG-CSF(按体质量50μg/kg)腹部皮下注射,假手术组和脑缺血再灌注组则予等量生理盐水。采用Longa 5分制标准评分法于术后24h进行神经功能评分,用免疫组化法检测各组大鼠脑组织p-JAK2及pSTAT3蛋白表达水平,用2,3,5-三苯基氯化四氮唑(TTC)染色法测定脑梗死体积,用原位末端转移酶标记(TUNEL)检测神经细胞凋亡情况。结果假手术组大鼠未见神经功能缺损,脑组织未发现梗死灶;治疗组梗死灶体积〔(16.27±1.44)%〕较缺血再灌注组〔(28.65±1.36)%〕明显减少(P<0.01),治疗组神经功能评分(1.45±0.51)低于缺血再灌注组(2.72±0.45;P<0.01)。缺血再灌注组p-JAK2、p-STAT3表达(灰度值分别为25.62±6.25、24.52±5.08)均低于假手术组(灰度值分别为41.59±6.43、43.36±5.68;均P<0.01)〕,治疗组p-JAK2及p-STAT3表达(灰度值分别为36.47±6.38、35.87±5.52)均较缺血再灌注组(灰度值分别为25.62±6.25、24.52±5.08)增高(均P<0.01);假手术组偶见细胞凋亡,治疗组凋亡细胞比例〔(27.84±2.69)%〕较缺血再灌注组〔(39.51±3.74)%〕明显减少(P<0.01)。结论 rhG-CSF可能对脑缺血再灌注损伤有神经保护作用,其机制可能为通过抑制炎性细胞因子介导JAK2/STAT3信号转导通路而减轻脑缺血再灌注引起的神经损伤。Objective To observe the expression of p-JAK2, p-STAT3, and cell apoptosis of the brain following cerebral ischemia/reperfusion （MCAO/R） in rats that were injected with recombinant human granulocyte colony-stimulating factor （rhG-CSF）, and to explore the neuroprotective mechanisms of rhG-CSF. Methods Thirty-six male Sprague-Dawley rats were randomly divided into the sham-operated group, the cerebral ischemia-reperfusion group, and the rhG-CSF-treatment group. And each group had 12 rats. The MCAO/R model was made by the Longa suture method. In the rhG-CSF-treatment group, rats were injected with a single dose of 50 μg/kg rhG-CSF subcutaneously at 2 h and 24 h after the reperfusion. The sham-operated group and cerebral ischemia-reperfusion group received the same volume of saline. The neurological function was scored with Longa 5-point scale 24 h after reperfusion. The expressions of p-JAK2 and p-STAT3 were detected by immunohistochemistry. The apoptosis cells were evaluated by TUNEL method. The infarction volume was revealed by TTC stain. Results Neurological function defects were hardly to be found and no infarction was observed in the rats of sham-operated group. The volume of infarction and neurological outcome scores of the rhG-CSF treatment group [ （16. 27±1.44）%, 1.45±0. 51] were lower than those of the ischemia-reperfusion group [ （28.65±1.36）%, 2. 72±0.45, P〈0.01, respectively]. The expressions of p JAK2 and p-STAT3 in the ischemia-reperfusion group （the gray values were 25.62±6.25 and 24.52 ± 5.08 respectively ） all deceased compared with the sham operated group （the gray values were 41.59 ±6.43 and 43.36 ±5.68, P〈0.01, respectively）. The expressions of p-JAK2 and p-STAT3 in the rhG-CSF-treatment group （the gray values were 36.47±6.38 and 35.87±5.52 respectively） significantly increased compared with the ischemia-reperfusion group （the gray values were 25.62±6.25 and 24.52±5.08, P〈0.01, respectively）. Apoptotic cells were hardly to be found in the sham op

关 键 词：缺血再灌注损伤 磷酸化酪氨酸激酶-2 磷酸化信号转导子和转录活化子-3 细胞凋亡 重组人粒细胞集落刺激因子 

分 类 号：R743.33[医药卫生—神经病学与精神病学]