过氧化物酶体增殖物激活型受体α不同激活物对HepG2细胞1型纤溶酶原激活物抑制剂表达的影响  

Effects of different activators of peroxisome proliferator-activated receptors alpha on the expression of plasminogen activator inhibitor-1 in human hepatoma cells

作　　者：陈静[1] 叶平[1] 刘永学[2] 贺艳丽[2] 

机构地区：[1]解放军总医院老年心血管二科,北京市100853 [2]解放军军事医学科学院,北京市100850

出　　处：《中国临床康复》2005年第31期112-115,共4页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(30470717)~~

摘　　要：目的:观察不同的过氧化物酶体增殖物激活型受体α对人肝瘤细胞1型纤溶酶原激活物抑制剂mRNA表达及其活性的影响,探讨过氧化物酶体增殖物激活型受体α在1型纤溶酶原激活物抑制剂基因调控中的作用。方法:实验于2004-04/2005-04在军事医学科学院放射医学研究所药理毒理实验室完成。分别以终浓度为50和100μmol/L的过氧化物酶体增殖物激活型受体α不同特异性激活物非诺贝特和亚油酸作用于人肝瘤细胞,设未加入非诺贝特和亚油酸作用于人肝瘤细胞为空白对照组。采用半定量反转录-聚合酶链式反应法检测人肝瘤细胞1型纤溶酶原激活物抑制剂及过氧化物酶体增殖物激活型受体α的mRNA水平,发色底物法检测1型纤溶酶原激活物抑制剂的活性变化。结果:①与空白对照组相比,非诺贝特组在50和100μmol/L浓度诱导下1型纤溶酶原激活物抑制剂mRNA表达分别减少31.97%,45.49%(P<0.05,0.01);亚油酸组在50和100μmol/L浓度诱导下1型纤溶酶原激活物抑制剂mRNA表达分别增加43.0%,129.0%(P<0.05,0.01)。②与空白对照组相比,非诺贝特组在50和100μmol/L浓度诱导下1型纤溶酶原激活物抑制剂蛋白活性分别降低39.3%,49.6%(P<0.01);亚油酸组在50和100μmol/L浓度诱导下1型纤溶酶原激活物抑制剂蛋白活性分别升高37.5%,112.6%(P<0.01)。与空白对照组相比,人肝瘤细胞过氧化物酶体增殖物激活型受体αmRNA表达量在非诺贝特组100μmol/L浓度诱导下明显增高79.79%(P<0.05),在亚油酸组50和100μmol/L浓度诱导下则分别显著增高46.73%(P<0.05),79.45%(P<0.01),非诺贝特组50μmol/L浓度诱导下使人肝瘤细胞过氧化物酶体增殖物激活型受体αmRNA表达量有升高趋势,但差异不明显。结论:过氧化物酶体增殖物激活型受体α激活物可以影响人肝瘤细胞1型纤溶酶原激活物抑制剂的基因转录及过氧化物酶体增殖物激活型受体αmRNA的表达,且均呈一定�AIM： To observe the effects of different activators of peroxisome proliferator-activated receptors alpha （PPARα） on mRNA expression and activity of plasminogen activator inhibitor-1 （PAI-1） in human hepatoma cells （HepG2） and discuss the effects of the PPARα in the regulation of PAI-1 gene. METHODS： The experiment was done in the laboratory of Pharmacology and Toxicology, Institute of Radiation Medical Science, Academy of Military Medical Sciences between April 2004 and April 2005. The different special activation of fenofibrate and linoleic acid in the PPARα at the final concentration of 50, 100 μmol/L had effects on the HepG2. The HepG2 that did not add with fenofibrate and linoleic acid was taken as vacant control group. The levels of mRNA of PAI-1 and PPARα were detected with the reverse transcriptase-polymerase chain reaction. The changes of PAI-1 activity were detected with the ehromogenic substrate method. RESULTS： ① Compared with the vacant control group, the mRNA expression of PAI-1 in the fenofibrate group with the concentration of 50, 100 μmol/L decreased 31.97%, 45.49%（P 〈 0.05, 0.01 ）, respectively. The mRNA expression of PAI-1 in the linoleic acid group with the concentration of 50,100 μmol/L increased 43.0%, 129.0% （P 〈 0.05, 0.01 ）, respectively. ② Compared with the vacant control group, the protein activity of PAI-1 in the fenofibrate group with the concentration of 50, 100 μmol/L decreased 39.3%, 49.6% （P 〈 0.01 ）, respectively. The protein activity of PAI-1 in the linoleic acid group with the concentration of 50, 100 μmol/L increased 37.5%, 112.6%（P 〈 0.01 ）, respectively. Compared with the vacant control group, the mRNA expression of PPARα in HepG2 in the fenofibrate group with the concentration of 100 μmol/L increased significantly 79.79%（P 〈 0.05）, and in the linoleic acid group with the concentration of 50, 100 μmol/L it increased significantly 46.73% （P 〈 0.05）, 79.45% （P 〈 0.01 ）, respectively. The mRNA expression

关 键 词：纤溶酶原激活物抑制物1 亚油酸 非诺贝特 

分 类 号：R54[医药卫生—心血管疾病]