非诺贝特抑制兔脂肪组织纤溶酶原激活物抑制剂-1表达的机制  

Study on the mechanism of fenofibrate-inhibited expression of plasminogen activator inhibitor-1 in adipose tissue from cholesterol-fed rabbits

作　　者：李洁琪[1] 赵水平[2] 吴洁[2] 李全忠[2] 方颖[1] 吴立荣[1] 蔡运昌[3] 李屏[1] 

机构地区：[1]贵阳医学院医科所心血管病研究室,贵州贵阳550004 [2]中南大学湘雅二医院心内科,湖南长沙410011 [3]贵州省人民医院心内科,贵州贵阳550004

出　　处：《中国医院药学杂志》2007年第1期13-16,共4页Chinese Journal of Hospital Pharmacy

基　　金：贵州省省长基金资助项目(编号:2005-224)

摘　　要：目的:观察非诺贝特对高胆固醇喂养兔脂肪组织纤溶酶原激活物抑制剂-1(PAI-1)mRNA表达的影响,并阐明其可能机制。方法:15只兔随机分为对照组、高胆固醇血症组和非诺贝特治疗组。实验的第12周末取兔皮下脂肪组织,并分离培养脂肪细胞,应用半定量逆转录多聚酶链式反应(RT-PCR)测定脂肪组织和细胞PAI-1、PPARγ和PPARαmRNA的表达。结果:高胆固醇血症组脂肪组织PAI-1mRNA表达高于对照组(P<0.01)。非诺贝特治疗后脂肪组织PAI-1mRNA表达明显低于高胆固醇组(P<0.01)。高胆固醇组脂肪组织PPARγmRNA表达高于对照组(P<0.05),非诺贝特能降低高胆固醇饲养兔脂肪组织PPARγmRNA表达(P<0.05),并呈剂量依赖性的降低脂肪细胞PAI-1和PPARγmRNA表达。3组兔脂肪组织PPARαmRNA表达差异无显著性。结论:非诺贝特能抑制高胆固醇饲养兔脂肪组织PAI-1mRNA表达,其机制可能与下调脂肪细胞PPARγmRNA表达有关。OBJECTIVE To investigate the influence of fenofibrate on plasminogen activator inhibitor-1 （PAI-1） expression in adipose tissue from rabbits with hypercholesterolemia and the mechanism possibly involved. METHODS 15 New Zealand rabbits were randomly divided into 3 groups： control group and hypercholesterolemia group and fenofibrate treatment group. At the end of 12^th week from the start of experiment, subcutaneous adipose tissue was collected under deep anesthesia, and culture adipocytes. The mRNA levels of PAI-1 and PPARa and PPARγ were evaluated by semi-quantitative reverse transcriptionpolymerase chain reaction （RT-PCR）. RESULTS The mRNA expression of PAI-1 was significantly increased in hypercholesterolemia group （P〈0. 01）. Fenofibrate obviously inhibited PAI-1 mRNA expression in adipose tissue （P〈0. 01 ）. The mRNA levels of PPAR7 in adipose tissue was increased in hypercholesterolemia group （P〈0. 05）. PPAR7 rnRNA levels were significantly lower in fenofibrate treatment group than in hypercholesterolemia group（P〈0. 05）. Fenofibrate decreased the expression of PAI-1 and PPAR7 in adipocytes, in a concentration- dependent manner. The PPARα mRNA expression was similar in adipose tissue of three groups. CONCLUSION Fenofibrate inhibits PAI-1 rnRNA expression in adipose tissue. The inhibition of PPARγ mRNA expression in adipose tissue and adipocytes may be involved in the downregulation of PAI-1 gene expression by fenofibrate.

关 键 词：非诺贝特 纤溶酶原激活物抑制剂-1 脂肪组织 过氧化体增殖物激活型受体 

分 类 号：R965[医药卫生—药理学]