比伐芦定对ApoE基因敲除小鼠动脉粥样硬化的影响

Effect of Bivalirudin on Atherosclerosis in Apolipoprotein E-knockout Mice

目的观察比伐芦定对Apo E基因敲除小鼠动脉粥样硬化的影响。方法将20只Apo E-/-小鼠随机分成模型组和治疗组,10只C57BL/6J小鼠作为空白对照组。模型组和治疗组给予高脂饲料喂养,空白组给予普通饲料喂养。于第9周开始,治疗组给予比伐芦定治疗4周。全自动生化分析仪检测血清中TG、TC、HDL-C、LDL-C含量,Elisa法检测各组小鼠血清TN F-α、IL-6水平变化,R T-PCR法检测主动脉VEGF、MMP-9、HIF-1αm R N A表达水平。结果与空白对照组比较,模型组小鼠血清TC、TG、LDL-C、TNF-α、IL-6水平显著升高(P<0.01),HDL水平显著降低(P<0.01),VEGF、MMP-9、HIF1-αm R N A表达水平显著升高(P<0.01);与模型组比较,治疗组小鼠血清水平、炎症因子水平以及VEGF、MMP-9、HIF1-αm R N A表达水平明显改善(P<0.01)。结论中药水蛭的有效成分水蛭素的人工合成药物比伐芦定能够通过改善血脂水平,血清炎症因子水平及血管新生等方面发挥良好的抗动脉粥样硬化作用。

Objective To study the effect of bivalirudin on atherosclerosis in ApoE-/-knockout mice.Methods Twenty ApoE-knockout mice were divided randomly into model group and treatment group.Ten C57BL/6J mice with same age and genetic backgmund were used as blank control group.Model group and treatment group were fed with high fat diet.The blank control group was fed nomal diet.The treatment group was given bivalirudin for 4 weeks from the 9th week.Determination of TG,TC,HDL-C and LDL-C in serum by automatic biochemical analyzer,TNF-αand IL-6 level were detected by ELISA.The expression level of VEGF,MMP-9 and HIF-1αmRNA in the aorta were detected by RT-PCR.Results Comparing with the blank control group,the levels of TC,TG,LDL-C,TNF-αand IL-6 in the model group were significantly increased(P<0.01),the HDL-C levels were significantly lower(P<0.01).The mRNA expression levels of VEGF,MMP-9 and HIF1-αwere significantly increased(P<0.01).Comparing with the model group,the serum level,levels of inflammatory factors and the expression levels of VEGF,MMP-9 and HIF1-αmRNA in the treatment group were significantly improved(P<0.01).Conclusion The active ingredient of leech,Hirudin artificial synthetic drugs-bivalirudin has a good anti-atherosclerotic effect,exerting anti-atherogenic effects by improving blood lipid levels,serum levels of inflammatory cytokines and angiogenesis.