β_3肾上腺素受体对前蛋白转化酶枯草溶菌素9和低密度脂蛋白受体表达的影响  

Effect of β_3-AR agonists on expression of PCSK9 and LDLR in apoE gene knock-out mice

作　　者：李艳芳[1] 蒋志丽[1] 郭彦青[1] 宋俊迎 

机构地区：[1]首都医科大学附属北京安贞医院急诊科,100029

出　　处：《中华老年心脑血管病杂志》2014年第6期627-629,共3页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金面上项目(81270380)

摘　　要：目的观察激动β3肾上腺素受体(β3-AR)对载脂蛋白E基因敲除(apoE-/-)老年高脂小鼠血脂、肝脏前蛋白转化酶枯草溶菌素9(PCSK9)和LDL受体(LDLR)表达水平的影响。方法选择10周龄雄性C57BL/6小鼠10只(A组)。apoE-/-小鼠40只给予高脂饲料饲养至36周龄,随机分为4组,分别为高脂模型组(B组)、阿托伐他汀阳性药物对照组(C组)、β3-AR激动剂小剂量组(D组)、β3-AR激动剂大剂量组(E组),每组10只,共干预12周。采用Beckman CX7全自动生化分析仪,检测血清TC、TG、VLDL/LDL-C、HDL-C水平,采用Western blot测定肝脏PCSK9和LDLR表达水平。结果与B组比较,C组、D组和E组TC、VLDL/LDL-C明显下降,C组、B组、D组LDLR水平明显上调,C组PCSK9水平明显上调(P<0.05,P<0.01);与C组比较,D组和E组TG、PCSK9水平明显下降,D组LDLR水平明显下降,HDL-C水平明显升高,差异有统计学意义(P<0.05,P<0.01)。结论β3-AR调脂、升高LDLR、降低PCSK9表达水平是其抗动脉粥样硬化的多重作用机制之一。Objective To study the effect of β3-AR agonists on expression of PCSK9 and LDLR in elderly apoE gene knock-out mice .Methods Ten male C57BL/6 mice aged 10 weeks served as group A and 40 apoE gene knock-out mice fed with high fat diet to 36 weeks old were randomly divided into high fat model group （group B） ,positive atrovastatin control group （group C） ,small doseβ3-AR agonist group （group D） and large dose β3-AR agonist group （group E） ,10 in each group .The animals were treated with atorvastatin and β3-AR agonists for 12 weeks .Serum levels of TC ,TG ,VLDL/LDL-C ,HDL-C were measured with the Beckman CX7 automatic biochemical analyzer and expression of PCSK9 and LDLR was detected by Western blot .Results The serum TC and VLDL/LDL-C levels were significantly lower in groups C ,D and E than in group B ,the expression level of LDLR was significantly higher in groups C ,B and D than in group E while that of PCSK9 was significantly higher in group C than in groups B ,D and E （P〈0 .05 ,P〈0 .01） .The serum TG level was significantly lower in groups D and E than in group C ,the expression level of LDLR was significantly lower while the serum HDL-C level was significantly higher in group D than in group C （P〈0 .05 ,P〈0 .01） .Conclusion β3-AR agonist decreases TC ,VLDL/LDL-C , TG levels and expression of PCSK9 ,and increases LDLR and HDL-C level ,which are one of its anti-atherosclerosis mechanisms in elderly apoE^-/-mice .

关 键 词：受体 肾上腺素能β3 载脂蛋白E类 前蛋白转化酶类 受体 LDL 降血脂药 

分 类 号：R965[医药卫生—药理学]