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血管内皮生长因子联合碱性成纤维细胞生长因子对大鼠后肢动脉硬化闭塞血管再生机制的研究

Study of Angiogenesis Mechanisms of Vascular Endothelial Growth Factor Combined with Basic Fibroblast Growth Factor for Arteriosclerosis Obliterans of Rat Hind Limb

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【作者】 杨婷王凯峰孙瑶刘彦辉王瀚锐范东旭金松窦鹏挥刘彦东

【Author】 YANG Ting;WANG Kai-feng;SUN Yao;LIU Yan-hui;WANG Han-rui;FAN Dong-xu;JIN Song;DOU Peng-hui;LIU Yan-dong;Department of Vascular Surgery,The First Affiliated Hospital of Jiamusi University;Department of Vascular Surgery,The Fourth Daqing City Hospital;

【机构】 佳木斯大学附属第一医院血管外科大庆市第四医院血管外科

【摘要】 目的探讨血管内皮生长因子(VEGF)联合碱性成纤维细胞生长因子(b FGF)对大鼠后肢动脉硬化闭塞血管再生的机制。方法雄性SD大鼠60只,建立后肢动脉硬化闭塞模型,按随机数字表法将其分为4组:生理盐水组(NS组)、VEGF组、b FGF组及VEGF+b FGF组。NS组、VEGF组隔天于腹腔分别注射生理盐水1 m L、100μg/L rh VEGF 1 m L;b FGF组隔天于后肢股内侧多点肌肉注射100μg/L rhb FGF 1 m L;VEGF+b FGF组隔天于腹腔注射100μg/L rh VEGF 1 m L及于后肢股内侧多点肌肉注射100μg/L rhb FGF 1 m L,共治疗21 d。第30 d时行血管造影检查观察大鼠后肢动脉硬化闭塞血管再生情况;第3个月时,取后肢股内侧肌肉组织分别应用Western blot和RT-PCR法检测其组织中VEGF和b FGF蛋白和m RNA表达水平。结果 1血管造影结果显示,VEGF+b FGF组侧支血管新生条数明显多于b FGF组(P<0.05)、VEGF组(P<0.05)及NS组(P<0.001),b FGF组和VEGF组也明显多于NS组(P<0.05),b FGF组和VEGF组间比较差异无统计学意义(P>0.05)。2 Western blot和RT-PCR检测结果均显示,VEGF和b FGF蛋白和m RNA表达在VEGF+b FGF组均明显高于NS组(P<0.001)、VEGF组(P<0.001)和b FGF组(P<0.001);VEGF组和b FGF组组间比较差异无统计学意义(P>0.05)。结论 VEGF和b FGF联合应用能够上调大鼠后肢缺血区组织中VEGF、b FGF的含量,促进血管内皮细胞增殖和分化、毛细血管出芽生长,使缺血区血管新生,为外周动脉疾病的临床治疗提供新方法。

【Abstract】 Objective To investigate the angiogenesis mechanisms of vascular endothelial growth factor(VEGF) combined with basic fibroblast growth factor(b FGF) for arteriosclerosis obliterans of rat hind limb. Methods The models of hind limb arteriosclerosis obliterans of 60 male SD rats were established and randomly divided into four groups: normal saline(NS) group, VEGF group, b FGF group, and VEGF+b FGF group. The saline 1 mL and 100 μg/L rh VEGF 1 mL were respectively injected into the abdominal cavity on every other day in the NS group and VEGF group. The 100 μg/L rhb FGF 1 mL was multiply injected into the hind limb medial vastus muscle in the b FGF group. The 100 μg/L rh VEGF 1 mL and 100 μg/L rhb FGF 1 mL were respectively injected into the abdominal cavity and the hind limb medial vastus muscle on every other day in the VEGF+b FGF group. The angiogenesis of rat hind limb arteriosclerosis obliterans was observed on day 30 by digital subtraction angiography(DSA). The VEGF and b FGF protein and m RNA expressions in the hind limb medial vastus muscle tissues were tested by the Western blot and RT-PCR methods respectively. Results1 The number of new collateral vessel in the VEGF+b FGF group was significantly more than that in the b FGF group(P<0.05), VEGF group(P<0.05), and NS group(P<0.001), which in the VEGF group or b FGF group was significantly more than that in the NS group(P<0.001), and which had no significant difference between the VEGF group and b FGF group(P>0.05). 2 The protein and m RNA expressions of VEGF and b FGF in the VEGF+b FGF group were significantly higher than those in the b FGF group(P<0.001), VEGF group(P<0.001), and NS group(P<0.001), which in the VEGF and b FGF were significantly higher than those in the NS group(P<0.001), which had no significant difference between the VEGF group and b FGF group(P>0.05). Conclusions VEGF and b FGF in combination could increase the expressions of VEGF and b FGF in the rat hind limb ischemia region tissue and promote vascular endothelial cell proliferation and differentiation, and capillary sprouting growth, make angiogenesis of ischemic area, it is provided a new clinical treatment of peripheral arterial disease.

【基金】 2014年度黑龙江省教育厅科学技术研究(面上)项目(编号:12541812)~~
  • 【文献出处】 中国普外基础与临床杂志 ,Chinese Journal of Bases and Clinics in General Surgery , 编辑部邮箱 ,2015年08期
  • 【分类号】R654.3
  • 【被引频次】13
  • 【下载频次】219
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