PCSK9单抗的应用对高脂模型小鼠血脂影响的实验研究  

Effects of anti-PCSK9 monoclonal antibody on blood lipid in hyperlipidemic mice

作　　者：张奕 

机构地区：[1]福建省福州鼓楼医院心血管内科,福州350001

出　　处：《福建医药杂志》2016年第2期76-78,共3页Fujian Medical Journal

摘　　要：目的观察前蛋白转化枯草杆菌/丝氨酸蛋白酶9(PCSK9)单抗在高脂模型小鼠降血脂方面的作用。方法高脂饲料喂养建立小鼠高脂模型,并采用不同剂量(0.25、0.5、1mg/kg)的PCSK9单抗进行静脉注射。全自动生化分析仪检测小鼠血清TC、TG、HDL-C、LDL-C水平,Western blot检测小鼠肝脏LDL受体(LDL-R)蛋白水平。结果模型组、PCSK9低、中、高剂量组TC、TG、LDL-C水平都明显高于空白组(P<0.05),HDL-C水平都明显低于空白组(P<0.05);PCSK9低、中、高剂量组TC、TG、LDL-C水平都明显低于模型组(P<0.05),HDL-C水平都明显高于模型组(P<0.05),且存在明显的剂量依赖性。另外,模型组、PCSK9低、中剂量组小鼠肝组织中LDL-R的表达水平明显低于空白组(P<0.05);PCSK9低、中、高剂量组小鼠肝组织中LDL-R的表达水平明显高于模型组(P<0.05)。结论 PCSK9单抗具有较好的降血脂作用,有望成为治疗心血管疾病的新药。Objective To investigate the effect of anti-PCSK9 monoclonal antibody on blood lipid in hyperlipidemic mice.Methods Hyperlipidemic mice model was established by fat diet.Then all mice except for control were intravenously injected with different doses（0.25,0.5,1mg/kg）of anti-PCSK9 monoclonal antibody.Serum TC,TG,HDL-C and LDL-C were analyzed by automatic biochemical analyzer.The expression of LDL-R in liver was detected by Western blot.Results Serum TC,TG and LDL-C in all groups were significantly higher than control group（P〈0.05）,while HDL-C was lower than control group（P〈0.05）.Serum TC,TG and LDL-C in different doses of PCSK9 groups were significantly lower than model group（P〈0.05）,while HDL-C was higher than model group（P〈0.05）,which showed as a dose-dependent manner.In addition,the expression of LDL-R in all groups but high dose of PCSK9 group were significantly lower than control group（P〈0.05）,and that in different doses of PCSK9 groups was significantly higher than model group（P〈0.05）.Conclusion Anti-PCSK9 monoclonal antibody has a good lipid-lowering effect,which is expected to become a new drug for treating cardiovascular disease.

关 键 词：PCSK9 单抗 血脂 LDL-R 

分 类 号：R589.2[医药卫生—内分泌] R-332[医药卫生—内科学]