吡格列酮对高脂饮食兔主动脉LOX-1表达的影响

Effects of Pioglitazone on expression of LOX-1 in aorta of high-cholesterol diet rabbits

目的探讨吡格列酮对高脂饮食下兔主动脉LOX-1表达的影响及其对动脉粥样硬化的作用。方法设立正常饮食、高脂饮食及高脂饮食加吡格列酮干预3组,通过比较主动脉病理形态学改变、血脂的变化、LOX-1分子及mRNA的表达进行研究,采用免疫组化检测兔主动脉LOX-1分子的表达,采用RT-PCR检测LOX-1mRNA的表达。结果吡格列酮能减轻高脂饮食所致的内膜增厚和平滑肌增生,减轻高脂血症所致动脉粥样硬化的发展。吡格列酮还能明显升高HDL,对TC、LDL、TG和BS无明显影响。高脂饮食刺激兔主动脉LOX-1分子及mRNA的表达,吡格列酮能显著减轻这种作用。结论吡格列酮能减轻高脂饮食兔主动脉LOX-1分子及mRNA的表达,这可能是噻唑烷酮类药物抗动脉粥样硬化的重要作用机制。

[Objective] To explore the effects of Pioglitazone on atherosclerosis and the expression LOX-1 in aorta of rabbits fed with high-cholesterol diet. [Method] 15 male healthy New Zealand rabbits were randomly divided into three groups： control group（n =5）was fed with normal diet for eight weeks; high cholesterol group（n =5） was fed with high-cholesterol diet for eight weeks; Pioglitazone treatment group（n =5） was fed with high-cholesterol diet for eight weeks supplemented with Pioglitazone（3 mg/kg·d） from the fourth week of cholesterol diet. The aortic pathological menifestation and plasma lipid in these groups were compared. LOX-1 molecule was detected by immunohistochemistry, LOX-1 mRNA was evaluated by reverse transcription-polymerase chain reaction（RT-PCR）. [Results] Pioglitazone decreased aortic intimal hyperplasia and smooth muscle cell proliferation in rabbit fed with high-cholesterol diet. Pioglitazone can also increase high density lipoprotein and decrese the expression of LOX-1 molecule and LOX-1 mRNA in the aorta of hypercholesterolemia rabbits aortic. [Conclusion] Pioglitazone can inhibit the upregulation of LOX-1 molecule and mRNA in the aorta of hypercholesterolemia rabbits. These observations provide novel insight into a potential antiatherosclerosis pathway of Thiazolidinediones.