氨氯地平对糖尿病载脂蛋白E基因敲除小鼠CD55和CD59表达的影响

Effects of amlodipine on expression of CD55 and CD59 on aorta in streptozotocin-induced diabetic apoE-knock out mice

目的观察糖尿病载脂蛋白E基因敲除小鼠主动脉组织中CD55、CD59表达变化及氨氯地平对其表达的影响。方法 32只雄性6周龄载脂蛋白E基因敲除小鼠随机分为动脉粥样硬化(AS)组10只、糖尿病AS组(D-AS组)12只、氨氯地平干预组(D-AM组)10只。监测生化指标,测量AS斑块面积;采用免疫荧光和实时定量PCR法检测蛋白和mRNA的变化,观察氨氯地平对CD55和CD59表达的影响。结果与AS组比较,D-AS组体重明显下降,差异有统计学意义(P<0.01),血糖、TC及LDL-C明显升高,差异有统计学意义(P<0.01),平均AS斑块面积增加,差异有统计学意义(P<0.05)。与D-AS组比较,D-AM组体重增加,差异有统计学意义(P<0.01),平均AS斑块面积减少,差异有统计学意义(P<0.01)。免疫荧光显示,与AS组比较,D-AS组CD55和CD59表达减弱;与D-AS组比较,D-AM组CD55和CD59表达增强。结论糖尿病载脂蛋白E基因敲除小鼠主动脉组织中CD55和CD59蛋白水平表达可能下调;独立于降压作用之外,氨氯地平可能具有上调CD55和CD59蛋白表达的作用。

Objective To investigate the levels of CD55 and CD59 expression on aortas, and the effects of amlodipine on diabetic atherosclerotic mice. Methods Thirty-two male apoE-knock out mice were obtained at 6 weeks of age. After 1 week of acclimatization, animals were divided into three groups ： atherosclerotic（AS） group（n = 10）, diabetic atherosclerotic（D-AS） group（n = 12）, and amlodipine（D-AM）group（n = 10）. Venous bloods were collected for analysis of glucose and lipids,and aortas were prepared for atherosclerotic plaques, immunofluorescence and real-time PCR. Results Compared with AS group,the body weight was decreased,and glucose,TC,LDL-C and atherosclerotic plaques were increased in D-AS group （P〈 0.01）. Compared with D-AS group,the body weight was increased,and atherosclerotic plaques were decreased in D-AM group （P〈0.01）. Immunofluorescence showed that expression of CD55 and CD59 was lower in D-AS group than that in AS group, and was higher in D-AM group than that in D-AS group. Conclusions The protein expression levels of CD55 and CD59 on aortas in diabetic apoE-knock out mice might be lower than that in apoE-knock out mice. After treatment with amlodipine, protein expression of CD55 and CD59 could be upregulated,independent of the effect on blood pressure in diabetic apoE-knock out mice.