GM-CSF在兔动脉粥硬化非梗死模型颅内血管生成中的作用及其机制的探讨

GM-CSF induces brain angiogenesis in non-infarct atherosclerosis rabbit models:the role and mechanism study

目的观察预防性给予"兔动脉粥硬化非梗死模型"GM-CSF治疗诱导颅内血管生成后,是否可以改善全脑血液循环状态,同时对其可能的调节机制进行初步探讨。方法 40只雄性新西兰大白兔随机分为对照组(ctr)、动脉粥样硬化组(AS)、生理盐水治疗组(NS)、GM-CSF治疗组(GM-CSF),每组10只,各组均进行右侧锁骨下动脉椎动脉开口近端结扎手术。先检测脑血管血液动力学指标(CVHI)的变化。再利用Western Blot检测缺血敏感区域脑组织血管内皮生长因子(VEGF)及色素上皮衍生生长因子(PEDF)蛋白的表达情况。结果 CVHI检测显示,GM-CSF组较AS组及NS组颈动脉Vmin有所增快(P<0.01),同时,GM-CSF组的Wv和Rv值较AS及NS组显著降低(P<0.01)。AS和NS组的缺血敏感区域脑组织PEDF、VEGF蛋白的表达较ctr组均有所增加(P<0.01);GM-CSF组PEDF表达较AS及NS组明显被抑制(P<0.01),而GM-CSF组VEGF蛋白的表达则高于其他3组(P<0.05)。结论预防性皮下注射GM-CSF,可以促进兔动脉粥样硬化非梗死模型颅内血管生成及侧枝循环的建立,进而改善全脑血液循环状态。另外,本研究发现,GM-CSF可能干预了血管平衡系统中关键因子PEDF及VEGF的表达。这可能是GM-CSF诱导颅内血管生成的重要的机制之一。

Objective To investigate changes of cerebrovascular hemodynamic index（CVHI） after GM-CSF treatment,and researched the regulative mechanism of GM-CSF in angiogenesis.Methods Male rabbits（n=40） were divided into four groups：control group（ctr）,atherosclerosis model group（AS）,atherosclerosis model plus normal saline treatment group（NS）,and atherosclerosis model plus GM-CSF treatment group（GM-CSF）.All rabbits were examined with CVHI.The pigment epithelium derived growth factor（PEDF） and vascular endothelial growth factor（VEGF） in brain tissue were detected by Western blot.Results It was showed that Vmin was improved in GM-CSF group compared to AS and NS groups（P〈0.01）.Wv and Rv were significantly decrease in GM-CSF group（P〈0.01）.Moreover,PEDF and VEGF protein expression in cerebral watershed region was increased in AS and NS group compared to control group（P〈0.01）.PEDF expression in GM-CSF group was significantly decreased compared to AS and NS group（P〈0.01）.VEGF expression in GM-CSF group was increased compared to other three groups（P〈0.05）.Conclusions It can be concluded that preventive subcutaneous injection of GM-CSF could induce angiogenesis in non-infarct atherosclerosis rabbit models,increase the ischemic sensitivity of brain area and improve cerebral circulation.In addition,GM-CSF could affect PEDF and VEGF protein expression of angiogenesis balance system,which may be one of the important mechanisms of angiogenesis induced by GM-CSF.