粒细胞集落刺激因子对脑缺血再灌注大鼠的治疗及其作用机制的研究
摘要
本研究旨在观察粒细胞集落刺激因子(G-CSF)对脑缺血再灌注损伤的治疗,并进一步研究其作用机制。首先,通过观察经G-CSF治疗脑缺血再灌注大鼠的体重变化、死亡率、梗死面积及HE染色,判定G-CSF可以减小脑梗死面积及动物死亡率,具有治疗作用。其次,应用免疫组织化学法测Bcl-2、Caspase-3、IL-1β、NF-κBp65、TUNEL法检测神经细胞凋亡。结果:NF-κBp65、IL-1β、Caspase-3三种阳性细胞和TUNEL细胞在各时间点脑缺血再灌注组增加,与假手术组相比,差异有统计学意义,粒细胞集落刺激因子治疗组,各类阳性细胞及凋亡细胞较手术组明显减少,差异有统计学意义。Bcl-2则在脑缺血再灌注组减少,应用G-CSF后上调。说明G-CSF在脑缺血再灌注后具有抗凋亡、抗炎作用,以发病24h效果最为显著。最后,通过建立脑缺血再灌注大鼠缺血皮层的差异表达蛋白质图谱,为进一步研究脑缺血再灌注的发生机制提供线索,成功建立脑缺血再灌注组和G-CSF治疗组大鼠大脑皮层蛋白质双向电泳图谱,寻找到脑缺血再灌注组与G-CSF治疗组的差异蛋白质,鉴定差异蛋白,确定G-CSF治疗脑缺血的部分靶蛋白,从蛋白质组学层面对G-CSF治疗脑缺血提供科学依据。
Cerebral vascular disease(CVB)is one of three most threaten disease to people’s lives and health. As so far, there is no effective method to cure the death of neuron. It’s important to protect the ischemic neuron and make neuron regenerate. It provide a new method to cure the cerebral infarction by studying the protective effect and mechanism of granulocyte colony-stimulating factor(G-CSF) to ischemia-reperfusion injury in rats brain. We use proteomics to research difference protein of Ischemia-reperfusion Injury in Rats Brain after curing by G-CSF, which further indicate the therapeutical effect mechanism of G-CSF.
At first, we testify the protective effect to Ischemia-reperfusion Injury in Rats Brain. The transient middle cerebral artery occlusion models were applied and reperfused after 2 hours. G-CSF (50ug/kg/d) is injected subcutaneously on rats’backs for successive 5 days. Rats was executed and decapitated receptively after 24h,7d and 14d after reperfusion to get the brain. The results of TTC stain show that and there is cerebral infarction in both brain of ischemia-reperfusion injured rats (I/R group) and the rats cured by G-CSF (G group). There is significant difference between the I/R group and G group, which testify the therapeutic effect of G-CSF. The results of HE stain confirms the results above again.
Secondly, immunohistochemical method and TUNEL stain are used to test Bcl-2、Caspase-3、IL-1β、NF-κBp65 and apoptosis. Results: It is hardly to see positive cells of each kind and apoptotic cells in N and S group. All kinds of positive cells and apoptotic cells are seen in I/R group, and there is significant difference between I/R and S group. All kinds of positive cells and apoptotic cells are significantly reduced in G group by contrast to I/R group.
At last, to research difference protein of ischemia-reperfusion injury in rats brain after curing by G-CSF and to screen relative protein of neuron protective effect by proteomics technology. Result: Compared with I/R group, the S group gained 56 differential protein spots, 17 spots expressed lowly, and 39 spots high, identified 19 protein spots,found out the relative cerebral ischemic proteins. Compared with I/R group, the G group gained 15 differential protein spots,3 spots expressed lowly,and 13 spots high,identified 6 protein spots, It’s found out the relative protective proteins of G-CSF such as GFAP, endomucin and DRP-2 etc.
Conclusion: In this experiment, it is proved that the neuron protective effect of G-CSF exists and G-CSF has a anti-apoptotic and anti-inflammatory effect to ischemia-reperfusion Injury in Rats Brain. By using proteomics, we know some proteins about cerebral ischemia , which further explore the mechanism of therapeutic effect of G-CSF .
Cerebral vascular disease(CVB)is one of three most threaten disease to people’s lives and health. As so far, there is no effective method to cure the death of neuron. It’s important to protect the ischemic neuron and make neuron regenerate. It provide a new method to cure the cerebral infarction by studying the protective effect and mechanism of granulocyte colony-stimulating factor(G-CSF) to ischemia-reperfusion injury in rats brain. We use proteomics to research difference protein of Ischemia-reperfusion Injury in Rats Brain after curing by G-CSF, which further indicate the therapeutical effect mechanism of G-CSF.
At first, we testify the protective effect to Ischemia-reperfusion Injury in Rats Brain. The transient middle cerebral artery occlusion models were applied and reperfused after 2 hours. G-CSF (50ug/kg/d) is injected subcutaneously on rats’backs for successive 5 days. Rats was executed and decapitated receptively after 24h,7d and 14d after reperfusion to get the brain. The results of TTC stain show that and there is cerebral infarction in both brain of ischemia-reperfusion injured rats (I/R group) and the rats cured by G-CSF (G group). There is significant difference between the I/R group and G group, which testify the therapeutic effect of G-CSF. The results of HE stain confirms the results above again.
Secondly, immunohistochemical method and TUNEL stain are used to test Bcl-2、Caspase-3、IL-1β、NF-κBp65 and apoptosis. Results: It is hardly to see positive cells of each kind and apoptotic cells in N and S group. All kinds of positive cells and apoptotic cells are seen in I/R group, and there is significant difference between I/R and S group. All kinds of positive cells and apoptotic cells are significantly reduced in G group by contrast to I/R group.
At last, to research difference protein of ischemia-reperfusion injury in rats brain after curing by G-CSF and to screen relative protein of neuron protective effect by proteomics technology. Result: Compared with I/R group, the S group gained 56 differential protein spots, 17 spots expressed lowly, and 39 spots high, identified 19 protein spots,found out the relative cerebral ischemic proteins. Compared with I/R group, the G group gained 15 differential protein spots,3 spots expressed lowly,and 13 spots high,identified 6 protein spots, It’s found out the relative protective proteins of G-CSF such as GFAP, endomucin and DRP-2 etc.
Conclusion: In this experiment, it is proved that the neuron protective effect of G-CSF exists and G-CSF has a anti-apoptotic and anti-inflammatory effect to ischemia-reperfusion Injury in Rats Brain. By using proteomics, we know some proteins about cerebral ischemia , which further explore the mechanism of therapeutic effect of G-CSF .
引文
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