血小板活化因子受体拮抗剂WEB2086抑制载脂蛋白E基因敲除鼠主动脉粥样硬化斑块内血管新生  

Platelet Activating Factor Receptor Antagonists WEB2086 Inhibits Angiogenesis in Atherosclerotic Plaque of Apolipoprotein E Gene Deficient Mice

作　　者：王双[1] 杨永宗[2] 唐雅玲[2] 易光辉[2] 唐朝克[2] 孙玉惠[2] 叶旭[2] 万载阳[2] 任重[2] 

机构地区：[1]中南大学湘雅医学院病理生理系,湖南省长沙市410078 [2]南华大学心血管病研究所,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2005年第2期143-145,共3页Chinese Journal of Arteriosclerosis

基　　金：国家 973项目 (G2 0 0 0 0 5690 5)资助

摘　　要：目的　观察血小板活化因子受体拮抗剂WEB2 0 86对载脂蛋白E基因敲除鼠斑块内血管新生和斑块面积的影响。方法　8周龄雄性载脂蛋白E基因敲除鼠普通饲料喂养2 4周,然后随机分为对照组和WEB2 0 86组2组,每组18只。两组均普通饲料,对照组普通饮水,WEB2 0 86组则在普通饮水中加入血小板活化因子受体拮抗剂WEB2 0 86 (43mg/L)。继续喂养8周后,空腹18h采血,安乐死,取材。全自动生物化学分析仪检测血清脂质含量,CD31全层铺片检测斑块内毛细血管密度,含斑块的主动脉环置于matrigel中培养检测斑块新生毛细血管的能力,苏丹Ⅳ染色检测斑块面积。结果　WEB2 0 86对血清脂质无明显影响。WEB2 0 86明显抑制粥样斑块内毛细血管平均密度(34.6 %±10 .2 %比16 .1%±6 .7% ,P <0 .0 1)、明显抑制含斑块的主动脉环在matrigel中新生毛细血管(172 .3±4 0 .6比73.1±2 4 .9,P <0 .0 5 )、显著减小主动脉斑块面积(31.4 %±9.7%比17.5 %±6 .3% ,P <0 .0 1)。结论　WEB2 0 86对血脂无明显影响,但可抑制斑块内血管新生和减小斑块面积。Aim To investigate the effect of platelet activating factor receptor (PAFR) antagonist on angiogenesis in plaque and lesion area of apolipoprotein E-deficient mice (apo E -/-). Methods 8-week-old male apo E -/- mice were fed a standard chow diet for 24 weeks to develop advanced lesions. Mice were then separated into the following two groups (n=18) and treated for 8 weeks: (1) chow diet with regular water, (2) chow diet with WEB2086 in the water (4.3 mg in 100 mL). Whole-Mount CD31 Stain and Plaque-Associated Sprouting have been used to estimate angiogenesis in plaque of aorta, Sudan Ⅳ staining to measure lesion area. Results Administration of WEB 2086 did not affect the lipid composition of mouse serum. However, lesion area was r significantly educed (31.4%±9.7% vs 17.5%±6.3%,P<0.01). The mean density of intimal capillarie of atherosclerotic plaque (34.6%±10.2% vs 16.1%±6.7%,P<0.01) and the mean number of sprouts per ring were significantly reduced in the WEB2086 group (172.3±40.6 vs 73.1±24.9,P<0.05). Conclusions These studies provide evidence that WEB2086 can inhibits angiogenesis in atherosclerotic plaque and reduce lesion area of apolipoprotein E-deficient mice.

关 键 词：病理学与病理生理学 血小板活化因子受体拮抗剂 WEB2086 血管新生 动脉粥样硬化斑块 

分 类 号：R363[医药卫生—病理学]