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出 处:《中国药物与临床》2006年第1期48-51,共4页Chinese Remedies & Clinics
摘 要:目的探讨吡格列酮对氧化低密度脂蛋白(oxLDL)刺激下的人脐静脉内皮细胞(HUVECs)CD40/CD40L表达的影响。方法原代培养人脐静脉内皮细胞,给予oxLDL刺激和不同浓度吡格列酮干预。采用流式细胞技术检测CD40/CD40L在细胞上的表达,采用反转录-聚合酶链反应(RT-PCR)检测LOX-1mRNA的表达。结果OxLDL以浓度和时间依赖的方式刺激HUVECs表达CD40/CD40L,吡格列酮以剂量依赖的方式减轻ox-LDL刺激HUVECs表达CD40/CD40L。同时我们还观察到oxLDL能刺激HUVECs上调LOX-1mRNA的表达,而吡格列酮能明显抑制这种作用。结论吡格列酮能减轻oxLDL刺激下的人脐静脉内皮细胞CD40/CD40L的表达,其作用的机制可能与其抑制了HUVECs的LOX-1受体表达有关。Objective The CD40/CD40 Hgand pathway mediates inflammatory processes important in athemgenesis and the formation of the intraplaque lipid pooLIt was evaluated that the hypothesis pioglitazone decrease CD40/CD40L expression in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (oxLDL). Method HUVECs were incubated with oxLDL for different time periods and vary concentrations to determine the expression of CD40/CIMOL.HUVECs were also incubated with oxLDL ( 80 u g/ml ) for 24 hours with or without pretreated by pioglitazone.Expression of CD40/CD40L were detected by flow cytometric technology, and LOX-1 mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR).Results It was observed that ox-LDL increased the expression of CD40 and CD40L in a concentration-and time-dependent manner.Pioglitazone can decrese the upregulation of CD40/CD40L on HUVECs induced by ox-LDL. A high concentration of pioglitazone (10 umol/L) had a greater effect than the low concentration (1 u mol/L).We also observed that ox-LDL upregulated LOX-1 mRNA expression on HU- VECs and pioglitazone can inhibited the effect in a dose-dependent manner, incubation of HUVECs with pioglitazone (10 u mol/L) alone did not affect CD40/CD40L and LOX-1 mRNA expression.Conclusion Lox-1 may play important roles in oxLDL uptake and subsequent functional alteration in the luminal endothelium in early atherosclerosis. Pioglitazone can inhibite the upregulation of LOX-1 in HUVECs elicited by oxLDL and subsequently decrease HUVECs CD40/CD40L expression induced by oxLDL These observation provide novel insigh into a potential novel antiinflammatory pathway of thiazolidinediones.
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