血管内皮生长因子165与动脉粥样硬化兔血清C反应蛋白水平的相关性

Vascular endothelial growth factor 165 in association with serum C-reactive protein level in rabbits with atherosclerosis

目的:观察内皮细胞生长因子165对兔血清C反应蛋白的影响,探讨其对动脉粥样硬化形成与发展的影响。方法:实验于2002-04/2004-06在郧阳医学院实验动物中心和生命科学研究所完成。15只日本大耳白兔随机分为3组:对照组给普通饲料喂养,高脂组及血管内皮生长因子组给高胆固醇饲料喂养,喂养21d后对照组及高脂组肌注白蛋白(2μg/kg),血管内皮细胞生长因子组肌注内皮细胞生成因子165(2μg/kg),继续以前方式饲养3周(喂养42d)处死动物,测定各组血清C反应蛋白和血脂水平,用计量组织学的方法(CD34的阳性面积)测定动脉粥样斑块内新生血管的密度。结果:实验兔3组15只均进入结果分析。①血清C反应蛋白浓度:喂养21d及42d时,高脂组和血管内皮细胞生长因子组分别高于对照组[21d:(1.57±0.3),(1.48±0.2),(0.38±0.1)mg/L,P<0.05;42d:(1.49±0.2),(2.81±0.9),(0.37±0.1)mg/L,P<0.05],血管内皮细胞生长因子组42d高于21d(P<0.01)。②喂养42d时新生血管的密度:CD34阳性细胞数血管内皮细胞生长因子组高于高脂组,且两组均高于对照组[(61.15±7.55),(12.35±2.02),0个/mm2,P<0.05]。③血清C反应蛋白浓度与CD34的阳性细胞数之间关系:呈正相关(r=0.944)。④斑块面积,斑块周径及斑块的最大厚度:血管内皮细胞生长因子组高于高脂组,且两组均高于对照组[斑块面积:(24.12±3.58),(1.81±0.61)%,0;斑块周径:(25.71±1.97),(6.05±1.62)%,0;斑块的最大厚度:(0.16±0.007),(0.06±0.002),0mm,P<0.05]。⑤电镜观察新生血管:新生血管与动脉粥样斑块相邻,新生管腔内可见淋巴细胞。结论:内皮细胞生成因子165促进斑块内血管生成的过程中,其促进C反应蛋白合成可能是其促进动脉粥样斑块形成与发展的作用之一。

AIM： To observe the effect of vascular endothelial growth factor （VEGF） 165 on levels of serum C-reactive protein （CRP） in rabbit and explore its effects on formation and development of atherosclerosis. METHODS： The experiment was conducted at the experimental animal center and Institute of Life Science of Yunyang Medical College from April 2002 to June 2004. Fifteen flap-eared Japanese rabbits were assigned randomly into 3 groups： The rabbits in the control group were given common feed. Those in the high-lipid group and VEGF group were feed with highcholesterol. After feeding for 21 days, those in the control group and highlipid group were injected with albumin into muscles （2 μg/kg）. Those in the VEGF group were injected with VEGF165 into muscles and killed after feeding for 3 weeks （feeding for 42 days） as before. The serum CRP and level of blood lipid were detected in every group. Density of new vessel in arterial atheromatous plaque was detected with measurement and histology method （CD 34 positive area）. RESULTS： Totally 15 experimental rabbits in the 3 groups were involved in the result analysis. （1） Concentration of serum CRP： When fed for 21 days and 42 days, it was higher in the high-lipid group and VEGF group than that in the control group [21 days：（1.57±0.3）, （1.48±0.2）, （0.38 ±0.1 ） mg/L,P 〈 0.05 ;42 days： （1.49±0.2）,（2.81±0.9）,（0.37±0.1） mg/L, p 〈 0.05]. It was higher in the VEGF group at 42 days than that at the 21 days （P 〈 0.131）. （2） Density of new vessel when fed for 42 days： Number of CD 34 positive cells in the VEGF group was higher than that in the highlipid group, and these two were all higher than that in the control group [（61.15±7.55）, （12.35±2.02）, 0/mm^2,P 〈 0.05]. （3） Relation between concentration of serum CRP and number of CD 34 positive cells： It showed positive correlation （r=0.944）. （4） Area of plaque, circumference and maximum depth of plaque： It was higher in the VEGF group than that in the high-lipid group, and these two groups were both higher than that in the control group [area of plaque： （24.12±3.58）, （1.81±0.61）%,0;circumference： （25.71 ±1.97）, （6.05±1.62）% ,0;maximum depth of plaque： （0.16 ±0.007）, （0.06±0.002）,0 mm,P 〈 0.05]. （5） New vessel observed by electron microscope： The new vessel was close to arterial athemmatous plaque. There were lymphocytes in the new cavity. CONCLUSION： VEGF165 increases angiogenesis in plaque. It accelerates CRP synthesis, which may be one of the factors of accelerating formation and development of arterial athemmatous plaque.