Zhao Shui-Ping, Li Jieqi, Xu Zhumei, Wu Jie, Li Quanzhong, Ye Huijun
Department of Cardiology, The Second XiangYa Hospital of Central South University, Changsha, Hunan 410011, PR China.
Clin Chim Acta. 2004 Nov;349(1-2):81-6. doi: 10.1016/j.cccn.2004.06.004.
Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in obesity. We investigated TF and PAI-1 mRNA expression in adipose tissues of cholesterol-fed rabbits, and the effects of fenofibrate.
Male rabbits were fed either a normal or high-cholesterol diet for 8 weeks. After 4 weeks, those fed high-cholesterol diets were randomly assigned to 30 mg/kg/day fenofibrate and starch. At the end of 12 weeks, subcutaneous adipose was collected. The concentration of TF and PAI-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The plasma activities of TF and PAI-1 were determined with ELISA and chromogenic substrate method, respectively.
The atherogenic diet caused a consistent increase in serum concentrations of total cholesterol (TC) (p<0.05) and did not significantly affect serum triglyceride (TG) concentrations, and increased TF and PAI-1 mRNA expression in adipose tissues (1.149+/-0.014 and 1.200+/-0.012, respectively) as compared to the normal diet (1.034+/-0.011 and 1.098+/-0.013, respectively) (p<0.01). The plasma activities of TF [(74.4+/-28.8) ng/l] and PAI-1 [(15.6+/-1.9) x 10(3) AU/l] in high-cholesterol diet group were higher than those of normal diet group [(33.1+/-10.7) ng/l and (6.9+/-0.9) x 10(3) AU/l, respectively, p<0.05]. Four-week fenofibrate treatment resulted in significant decrease of TF (1.017+/-0.010) and PAI-1 mRNA (1.061+/-0.011, p<0.01), the plasma activity of TF [(40.3+/-12.2) ng/l, p<0.05] and PAI-1 [(7.5+/-1.5) x 10(3) AU/l, p<0.01] also decreased significantly, and the concentrations of lipids were not changed.
TF and PAI-1 mRNA expression and plasma activities increased in adipose tissue of cholesterol-fed rabbits. Fenofibrate reduced TF and PAI-1 expression and plasma activity in adipose, suggesting that fenofibrate treatment reduces thrombosis risk, and may have an antithrombotic effect independent of its lipid-lowering.
肥胖时组织因子（TF）和纤溶酶原激活物抑制剂-1（PAI-1）的活性和/或表达上调。我们研究了胆固醇喂养兔脂肪组织中TF和PAI-1 mRNA的表达以及非诺贝特的作用。
雄性兔分别给予正常饮食或高胆固醇饮食8周。4周后，将给予高胆固醇饮食的兔随机分为给予30mg/kg/天非诺贝特组和淀粉组。12周结束时，收集皮下脂肪。通过逆转录-聚合酶链反应（RT-PCR）检测TF和PAI-1 mRNA的浓度。分别用ELISA和发色底物法测定血浆中TF和PAI-1的活性。
致动脉粥样硬化饮食导致血清总胆固醇（TC）浓度持续升高（p<0.05），对血清甘油三酯（TG）浓度无显著影响，且与正常饮食相比，脂肪组织中TF和PAI-1 mRNA表达增加（分别为1.149±0.014和1.200±0.012）（正常饮食分别为1.034±0.011和1.098±0.013）（p<0.01）。高胆固醇饮食组血浆中TF[（74.4±28.8）ng/l]和PAI-1[（15.6±1.9）×10³AU/l]的活性高于正常饮食组[分别为（33.1±10.7）ng/l和（6.9±0.9）×10³AU/l，p<0.05]。非诺贝特治疗4周导致TF（1.017±0.010）和PAI-1 mRNA（1.061±0.011，p<0.01）显著降低；血浆中TF[（40.3±12.2）ng/l，p<0.05]和PAI-1[（7.5±1.5）×10³AU/l，p<0.01]的活性也显著降低，且血脂浓度未改变。
胆固醇喂养兔的脂肪组织中TF和PAI-1 mRNA表达及血浆活性增加。非诺贝特降低了脂肪组织中TF和PAI-1的表达及血浆活性，提示非诺贝特治疗可降低血栓形成风险，且可能具有独立于其降脂作用的抗血栓作用。
