摘要
目的观察大脑中动脉栓塞模型转基因小鼠中bcl-xl的过表达对脑缺血后再灌流的保护作用及其机制。方法建立bcl-xl过表达转基因小鼠模型,将该模型小鼠与同种系野生型小鼠同时行线栓永久性阻塞大脑中动脉,在缺血24 h时测其神经功能评分,观察转基因小鼠与野生型小鼠的差别。在缺血后不同时间点分别检测两种小鼠梗死体积及其动态变化、脑组织中bcl-xl的表达量的差异、再灌流时凋亡细胞的数量和分布情况以及脑中细胞色素C及caspase-3的表达量及分布情况。结果转基因小鼠的神经功能评分低于野生型小鼠。在缺血后不同时间点,转基因小鼠的梗死体积小于并且皮质缺血区内的凋亡细胞数明显少于野生型小鼠,且保护作用发生时间早,持续时间较长。梗死前后转基因小鼠的皮质细胞bcl-xl的表达量均明显高于野生型小鼠,且梗死后两种小鼠体内的bcl-xl的表达量均有所增加,但两者之间差异无统计学意义(P>0.05)。缺血后再灌流后不同时间点,转基因小鼠缺血局部细胞色素C的表达及caspase-3的活化明显低于野生型小鼠。结论在规范化的标准条件下,转基因小鼠中bcl-xl基因的过表达能够降低脑梗死的体积并改善小鼠的神经功能。过表达bcl-xl基因的这种效应可能是通过抑制细胞凋亡而实现的,其机制可能是bcl-xl基因的过表达抑制了细胞色素C的释放及caspase-3的活化。
Objective To study the protective effects of bcl-xl overexpression on ischemia-repeffusion in the transgene rats with middle cerebral artery occlusion, and to study its mechanism. Method The model of bcl- xl overexpression in rats was produced. Middle cerebral artery occlusion was produced in this kind of rats and wild type rats. At 24 hours, the neurological function score was calculated to study the difference between two kinds of rats. The infarct area, the expression of bcl-xl before and after occlusion with immunohistechemistry, the number and distribution of apoptotic cells, and the expression of cytechrome C with Western-blot were detected at different time points after ischemia. Results The neurological function score, in transgene rats was lower than those in the wild type rots. The infarct area and the number of apoptotic cells were less in transgene rats, but protective effects happened earlier, and lasted for longer time. The expression of bcl-xl was obviously higher in transgene rats before and after infarct than that in wild type rats, and the expression of bcl-xl was increased in both kinds of rats after infarct, but there was no significant difference （ P 〉 0.05）. At different time points after ischemia-repeffusion, the expression of cytechrome C and activation of caspase-3 were lower in the transgen mice than that in the wild type rats. Conclusions Under standard condition, overexpression of bcl-xl could significantly reduce the infarct area and improve neurological function in transgene mice than those in the wild type rats. The effect of overexpression of bcl-xl might be realized through inhibiting the apoptosis of neuron, and the mechanism might be that the overexpression of bcl-xl inhibit the release of cytochrome C and the activation of caspase-3.
出处
《中华急诊医学杂志》
CAS
CSCD
2007年第9期917-920,共4页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金面上资助项目(30070825)
