阿托伐他汀对脂肪组织/细胞Ⅰ型纤溶酶原激活物抑制剂的影响

Effects of Atorvastatin on the Expression of Plasminogen Activator Inhibitor-1 in Adipose Tissues and Adipocytes

目的:观察高胆固醇喂养兔脂肪组织和脂肪细胞Ⅰ型纤溶酶原激活物抑制剂(PAI-1)表达及阿托伐他汀对其影响。方法:24只兔随机分为对照组、高胆固醇血症组和阿托伐他汀治疗组。实验末取兔皮下脂肪组织,并分离培养脂肪细胞,RT-PCR测定脂肪组织和脂肪细胞PAI-1mRNA表达;同时采血分离血浆,用发色底物法测定血浆PAI-1活性。结果:高胆固醇血症组血浆PAI-1活性与对照组比明显增加(P<0.01);该组脂肪组织和脂肪细胞PAI-1mRNA表达也明显高于对照组(P<0.01)。阿托伐他汀治疗后,该组脂肪组织和脂肪细胞PAI-1mRNA表达显著低于高胆固醇血症组(P<0.01),血浆PAI-1活性也明显降低(P<0.01)。结论:高胆固醇喂养兔脂肪组织和脂肪细胞表达PAI-1增加,血浆活性增强;阿托伐他汀能明显抑制高胆固醇喂养兔脂肪组织和脂肪细胞PAI-1表达及活性。

Objective： To investigate the effects of atorvastatin on mRNA expression of plasminogen activator inhibitor-1 （PAl-1 ）of adipose tissues and adipocytes in atherosclerotic rabbits. Methods： Twenty four male rabbits were randomly divided into three groups： control group, hypercholesterolemia group and atorvastatin treatment group. At the end of experiment, subcutaneous adipose tissues were collected under deep anesthesia. The adipocytes were then cultured. The levels of PAI-1 mRNA were tested by reverse transcription-polymerase chain reaction （RT-PCR）. The plasma PAI-1 activity level was determined with chromogenic substrate assay. Results： The expression of PAI-1 mRNA in adipose tissues and adipocytes and plasma activity of PAI-1 significantly increased in hypercholesterolemia group compared with that in control group （P 〈 0.01）. Compared with hypercholesterolemia group, atorvastatin significantly reduced the expression of PAl-1 mRNA of adipose tissues and adipocytes, and the plasma activity of PAI-1 in atorvastatin treatment group （P 〈 0.01）. Conclusion： The expressions of PAI-1 mRNA in adipose tissues and adipocytes were increased in atherosclerotic rabbits. The plasma PAI-1 activity level in atherosclerotic rabbits was also elevated. The results suggest that atorvastatin may have an antithrombtic affect by inhibiting PAI-1 expression in adipose tissues and adipocytes and decreasing the plasma PAI-1 activity level.