油酰乙醇胺通过过氧化物酶体增殖物激活受体α途径抑制单核-内皮细胞的黏附作用

Oleoylethanolamide inhibits monocyte-endothelial cell adhesion through peroxisome proliferator-activated receptor α pathway

目的探讨过氧化物酶体增殖物激活受体α(PPARα)激动剂油酰乙醇胺(OEA)对单核-内皮细胞黏附作用的影响。方法采用Western blot检测OEA对脂多糖诱导THP-1细胞中基质金属蛋白酶2(MMP-2)和MMP-9蛋白表达及对肿瘤坏死因子α(TNF-α)诱导人脐静脉内皮细胞中血管细胞黏附分子1(VCAM-1)和细胞间黏附分子1(ICAM-1)蛋白表达的影响。采用TNF-α诱导的单核-内皮细胞黏附模型,用PPARα阻断剂MK886阻断PPARα信号通路后,检测THP-1细胞的黏附和VCAM-1蛋白的表达。结果 40μmol/L OEA显著抑制MMP-2、MMP-9、VCAM-1和ICAM-1蛋白表达。OEA对TNF-α诱导的单核-内皮细胞黏附具有直接的抑制作用。MK886部分逆转了OEA对单核-内皮细胞黏附的抑制作用及对VCAM-1蛋白表达的抑制作用。结论 OEA能够抑制单核-内皮细胞的黏附,其机制可能与PPARα途径相关。

Aim To investigate the effect of peroxisome proliferator-activated receptor α( PPARα) agonist oleoylethanolamide( OEA) on the adhesion of monocytes to endothelial cells. Methods Western blot was used to detect the effects of OEA on the expressions of matrix metalloproteinase-2( MMP-2) and MMP-9 in lipopolysaccharide-induced THP-1 cells and the expressions of vascular cell adhesion molecule-1( VCAM-1) and intercellular cell adhesion molecule-1( ICAM-1) in human umbilical vein endothelial cells induced by tumor necrosis factor α( TNF-α). The adhesion of THP-1 cells and the expression of VCAM-1 protein were detected by TNF-α-induced monocyte-endothelial cell adhesion model after PPARα blocker MK886 blocked PPARα signaling pathway. Results 40 μmol/L OEA significantly inhibited MMP-2,MMP-9,VCAM-1 and ICAM-1 protein expression. OEA had a direct inhibitory effect on the monocyte-endothelial cell adhesion induced by TNF-α. MK886 partially reversed the inhibitory effect of OEA on monocyte-endothelial cell adhesion and VCAM-1 protein expression. Conclusion OEA can inhibit the adhesion of monocytes to endothelial cells,and its mechanism may be related to PPARα pathway.