【摘要】 目的探讨粒细胞集落刺激因子(G-CSF)预处理对心肌缺血/再灌注损伤的影响机制。方法25只健康家兔,随机分为3组:假手术对照组(Sham组,n=8),生理盐水组(NS组,n=9),G-CSF组(n=8)。Sham组开胸后心肌动脉只穿线不结扎;G-CSF组于术前连续5天皮下注射G-CSF 10μg.kg-1.d-11;NS组皮下注射生理盐水0.5 m l每日1次,连续5天;使用开胸法建立缺血/再灌注动物模型,光镜下观察各实验形态学改变,计数缺血区周边部毛细血管数量,免疫组化观察各组Bax、Bc l-2凋亡相关蛋白的表达,比较各组心肌细胞凋亡的程度。模型制备成功后,M acLab生理记录仪测定再灌注后左心室发展压(LVDP)及左心室内压最大上升和下降速率(+dp/dtm ax),比较各组间心功能差异。结果G-CSF组及NS组心功能均较Sham组下降(P(0.01),但G-CSF组心功能优于NS组(P(0.01)。G-CSF组缺血区周边部毛细血管计数高于NS组及Sham组(P(0.01)。G-CSF组Bc l-2明显高于NS组(P(0.01),Bax则明显低于NS组(P<0.01)。结论①G-CSF可以改善缺血/再灌注家兔的心功能;②G-CSF能够上调抗凋亡蛋白Bcl-2表达,同时抑制了促凋亡蛋白Bax的表达,减少了缺血急性期心肌细胞的凋亡;③G-CSF能够改善缺血心肌细胞的微循环,增加缺血区周边部毛细血管密度。更多还原

【Abstract】 Objective To investigate the mechanism of granulocyte colony-stimulating factor(G-CSF) preconditioning on myocardial ischemia/reperfusion(I/R) injury.Methods 25 healthy rabbits were randomly divided into three groups:(1) sham operation group(Sham group,n=8);opening the chest,with only threading under cardiac artery and without ligation.(2) NS group(n=9),subcutaneous injection of 0.5 ml normal saline for 5 days before I/R;(3) G-CSF group(n=8): subcutaneous injection of G-CSF(10 μg ·kg-1·d-1 for 5 days before I/R).After the animal model of I/R was established for observation of morphological changes and the capillary count with light microscopy and the expression of apoptosis-related proteins Bax and Bcl-2 with immunohistochemistry to compare the myocyte apoptosis in each group.After the animal model was prepared,the post-reperfusion LVDP and +dp/dtmax were determined by MacLab physiological recorder to compare the cardiac functional differences between each group.Results (1)Cardiac function in both NS group and G-CSF group was lower than that in Sham group(P<0.01),but was higher than in NS group(P<0.01).(2) The capillary count was higher in all the treatment groups with G-CSF than in NS group and the Sham group(P<0.01).(3) In the G-CSF group the expression of Bcl-2 protein was higher than that in the NS group and the Sham group(P<0.01),whereas the expression of Bax was markedly lower in G-CSF group than in the NS group(P<0.01).Conclusion(1) G-CSF could enhance cardiac function of rabbit after I/R injury.(2) G-CSF could upregulate the expression of the anti-apoptosis protein Bcl-2 and meanwhile restrain the expression of pro-apoptosis protein Bax,and decrease the myocyte apoptosis of acute ischemia.the extent of myocardial apoptosis in ischemia and reperfusion injury.(3) G-CSF could improve the microcirculation of ischemic myocytes and increase the density of peripheral capillaries in ischemic areas.更多还原