中文摘要：

目的探讨过氧化物酶体增殖物激活受体δ（peroxisome proliferator-activated receptorδ,PPARδ）在血管平滑肌细胞（vascular smooth muscle cells,VSMCs）泡沫化过程中的作用及可能机制。方法用组织贴块法体外培养原代VSMCs;用氧化型低密度脂蛋白（oxidized low density lipoprotein,ox-LDL）（50μg/m L）刺激VSMCs构建泡沫细胞模型,分为空白对照组及24、48、72 h组4组以检测VSMCs泡沫化过程中PPARδ的表达变化;利用PPARδ激动剂（GW0742,25 nmol/L）和抑制剂（GSK0660,1μmol/L）调控PPARδ并分为空白对照组、ox-LDL（50μg/m L）组、GW0742＋ox-LDL（50μg/m L）组、GSK0660＋ox-LDL（50μg/m L）组4组,刺激48 h;油红O染色及酶标仪测细胞内萃取油红光密度值检测细胞内脂质沉积;Western blot检测VSMCs中PPARδ、ACAT1蛋白表达情况以探索PPARδ在VSMCs泡沫细胞中的作用以及PPARδ和酰基辅酶A：胆固醇酰基转移酶1（A-cholesterol acyltransferase 1,ACAT1）的关系。结果 ox-LDL刺激下PPARδ的蛋白水平呈时间依赖地降低,其中48 h最低,下降约29%（P〈0.05）,随后维持在低水平表达;GW0742激动PPARδ后可明显减少VSMCs内总胆固醇含量约55%（P〈0.05）,而GSK0660则明显增加细胞内总胆固醇含量约20%（P〈0.05）;同时,GW0742可使ACAT1的蛋白表达量下降了约28%（P〈0.05）,而GSK0660则升高ACAT1的蛋白表达量约29%（P〈0.05）。结论 PPARδ的激活可通过下调ACAT1表达抑制血管平滑肌源性泡沫细胞的形成。

英文摘要：

Objective To identified the role of peroxisome proliferator-activated receptor δ（ PPARδ）and its possible mechanisms during the formation of vascular smooth muscle cells（ VSMCs）-derived foam cells. Methods Primary VSMCs were isolated from male C57 BL /6J mice by tissue attached methods.VSMCs were induced by oxidized low density lipoprotein（ ox-LDL） to form foam cells. The protein expression of PPARδ was detected by Western blotting in 24,48 and 72 h after ox-LDL treatment. Furthermore,PPARδagonist,GW0742（ 25 nmol / L）,and its inhibitor,GSK0660（ 1 μmol / L） were used to regulate PPARδ for the role of the molecule in the formation. VSMCs were treated respectively by ox-LDL（ 50 μg / m L）,GW0742 ＋ox-LDL（ 50 μg / m L）,and GSK0660 ＋ ox-LDL（ 50 μg / m L）,and the cells without treatment served as control. In 48 h after above treatment,Oil Red O staining was used to observe intracellular lipid deposition.Protein levels of PPARδ and acyl coenzyme A-cholesterol acyltransferase 1（ ACAT1） were determined by Western blotting,and then the levels were analyzed to explore the role of PPARδ during the formation of foam cells and its relationship with ACAT1. Results The protein level of PPARδs was reduced in a timedependent manner during the formation of foam cells derived from VSMCs,reached the lowest at the 48 th hour by 29% reduction（ vs control,P 〈 0. 05）,and then maintained at a low level. The addition of GW0742 obviously reduced the intracellular cholesterol content by about 55%（ vs ox-LDL group,P 〈 0. 05） in VSMCs,while GSK0660 significantly increased intracellular cholesterol content by about 20%（ vs ox-LDL group,P 〈 0. 05）. In addition,GW0742 treatment decreased the protein level of ACAT1 by about 28% 0%（ vs ox-LDL group,P 〈 0. 05）. However,GSK0660 elevated the level of ACAT1 by about 29%（ vs ox-LDL group,P 〈 0. 05）. Conclusion Activation of PPARδ suppresses the formation of foam cells from VSMCs by down-regulating the expression of ACAT1.