Vascular diseases such as atherosclerosis are characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal lining. The intimal VSMCs exhibit an increased expression of peroxisome proliferator-activated receptor (PPAR), and the administration of pharmacological PPAR agonists attenuates vascular lesion formation. The factors that regulate PPAR expression in the vasculature are poorly defined. Here we report that platelet-derived growth factor (PDGF) upregulates PPAR by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathway. Using Northern-blotting and Western-blotting analyses, we observed that the levels of PPAR mRNA and protein were increased by 2-to 3.5-fold in human aortic smooth muscle cells (HASMCs) treated with PDGF (20ng/mL). This was abolished by preincubation of HASMCs with a PI3-kinase inhibitor (LY294002, 50mol/L), and partially inhibited by a MEK1 inhibitor (U0126, 10mol/L), but not affected by a p38 kinase inhibitor (SB202190, 10mol/L). In addition, overexpression of the dominant-negative p85 subunit of PI3-kinase or Akt proteins blocked the PDGF-induced PPAR expression. Taken together, our results suggest that PDGF induces PPAR expression in VSMCs by a PI3-kinase/Akt signaling pathway. The characterization of factors and signaling pathways that modulate PPAR expression in VSMCs may have important implications for understanding the pathogenesis of vascular diseases.

目的 观察3种半离体体外肝手术方式对肝脏缺血再灌注损伤的影响。方法 SD大鼠随机分为对照组（A组）、单纯离断肝下下腔静脉手术组（B组）、单纯离断肝上下腔静脉手术组（C组）和联合离断肝上、肝下下腔静脉手术组（D组），每组各10只，手术后4、24h分组收集血清和肝组织，分别进行血清谷丙转氨酶（ALT）监测、病理切片、免疫组织化学和逆转录-聚合酶链反应（RT-PCR）检测。结果 ALT随各组手术复杂程度和再灌注时间的增加而升高；病理切片见各手术组肝脏炎症反应随手术复杂程度和再灌注时间的增加而有所加重；B组术后4和24h肝组织中过氧化物酶体增殖激活受体（PPAR）α的表达无明显变化，但术后24h原癌基因B淋巴瘤-xL（bclxL）的表达最强；C、D组肝组织术后4hPPARα和bcl-xL的表达增加，术后24hPPARα的表达明显强于4h组，而bcl-xL的表达较4h明显下降。结论 PPARα和bcl-xL参与体外肝手术后肝组织缺血再灌注损伤，两者的表达在一定程度上反应了肝细胞受损的程度。B组手术方式简单、对肝脏的损伤较小；C、D两组手术复杂，对肝组织的再灌注损伤较重。