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阿司匹林抑制ox-LDL诱导内皮细胞炎症分子表达的研究 被引量:8

Aspirin inhibition of expression of inflammatory proteins induced by oxidized low-density lipoprotein in HUVECs
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摘要 目的评价阿司匹林对ox-LDL刺激内皮细胞炎症蛋白表达的影响。方法使用培养人脐带内皮细胞,用氧化型低密度脂蛋白刺激内皮细胞16h,终止反应后用SDS-PAGE分离蛋白,使用Western Blot分析蛋白表达的变化。ROS测定使用DCFH-DA荧光标记,用流式细胞仪测定荧光强度。结果①阿司匹林抑制ox-LDL诱导内皮细胞COX-2表达。使用ox-LDL刺激内皮细胞16h,COX-2表达增加,分别用2.5mmol·L-1和5mmol·L-1阿司匹林处理内皮细胞30min后,COX-2表达明显降低。②阿司匹林降低ox-LDL诱导的内皮细胞ICAM-1表达。ox-LDL刺激内皮细胞16h后,Western Blot结果显示ICAM-1内皮细胞表达明显增加。用免疫荧光染色的方法观察细胞获得了同样的结果,ox-LDL刺激后ICAM-1在内皮细胞膜上表达明显增加,阿司匹林处理后减少了ICAM-1在膜上的表达。③阿司匹林轻度抑制ox-LDL诱导内皮细胞ROS产生。0.3g·L-1ox-LDL刺激内皮细胞16h后细胞内ROS明显增高,但阿司匹林仅部分阻止ROS的产生。结论非甾体类抗炎药物阿司匹林对ox-LDL诱导COX-2、ICAM-1有明显的抑制作用,但不能完全阻止ox-LDL诱导的ROS产生。这些结果表明阿司匹林能够减轻氧化脂质诱导的内皮细胞炎症损伤反应。 Aim To evaluate the effects of aspirin on the expression of inflammatory proteins induced by oxidized low-density lipoprotein (ox-LDL) in human vascular endothelial cells (HUVECs). Methods HU- VECs were stimulated with different concentrations of ox-LDL. The expression of inflammatory proteins was detected by Western blot. Intracellular ROS generation was measured by flow cytometry using perexide-sensitive flurscent probe 2', 7'-dichrofluorescein diacetate ( DCFH-DA ). Results ①Aspirin inhibited COX-2 expression induced by ox-LDL. Cells were preincubat- ed with 2. 5 mmol· L^-1, 5 mmol· L^-1 of aspirin or without any treatment for 30 min and then stimulated by 0. 3 g· L^-1 ox-LDL for 16 h, COX-2 expression was reduced by treating of aspirin. COX-2 expression was enhanced after the stimulation with ox-LDL, and aspirin inhibited the increasing. ② Aspirin suppressed ICAM-1 expression induced by ox-LDL in HUVECs. ICAM-1 expression was increased by ox-LDL stimulation for 16 h, and aspirin significantly down-regulated the expression. Similar results were obtained by immunofluorescence. ③ Aspirin partially reduced ROS production induced by ox-LDL in HUVECs. After stimulation with 0. 3 g·L^-1 ox-LDL for 16 h, the intracellular level of ROS was increased, however, aspirin failed to fully inhibit the phenomenon. Conclusion Nonsteroidal anti-inflammatory drugs (NSAID) aspirin significantly down-regulated the expression of COX-2 and ICAM-1 induced by ox-LDL. The results suggested that aspirin could reduce the inflammation responses mediated by ox-LDL on HUVECs in atherosclerosis.
出处 《中国药理学通报》 CAS CSCD 北大核心 2007年第4期472-475,共4页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No30471925)
关键词 阿司匹林 氧化型低密度脂蛋白 内皮细胞 aspirin oxidized low-density lipoprotein endothelial cell
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参考文献13

  • 1Bourcier T,Sukhova G,Libby P.The nuclear factor κB signaling pathway participates in dysregulation of vascular smooth muscle cells in vitro and in human atherosclerosis[J].J Biol Chem,1997,272(25):15817-24.
  • 2Hajra L,Evans A,Chen M,Hyduk S J.The NF-κB signal transduction pathway in aortic endothelial cells is primed for activation in region predisposed to atherosclerosis lesion formation[J].Proc Natl Acad Sci,2000,97(16):9052-7.
  • 3Maziere C,Auclair M,Djavaheri-Mergny M.Oxidized low dense lipoprotein induces activation of the transcription factor NF-κB in fibroblasts,endothelial cell,and smooth muscle cells[J].Biochem Mol Biol,1996,39(6):1201-7.
  • 4Bowie A,O'Neill L A.Oxidative stress and NF-κB activation:a reassessment of the evidence in the light of recent discoveries[J].Biochem Pharmacol,2000,59(1):13-23.
  • 5Jing Q,Xin S M,Cheng Z J,et al.Activation of 38 mitogen-activated pretein kinase by oxidized LDL in vascular smooth cells:mediation via pertussis toxin-sensitive G protein and association with oxidized LDL-induced cytoxicity[J].Circ Res,1999,84(7):831-39.
  • 6张斌,杜冠华.NSAIDs抗炎作用机制研究进展[J].中国药理学通报,2005,21(8):905-910. 被引量:18
  • 7Claudio N,Eric A,Filomena N,et al.Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density liboprotein oxidation and oxidative stress,arterial oxidation-specific epipes,and atherogenesis in hyperscholesterolemic mice[J].Proc Natl Acad Sci,2002,99(19):12467-70.
  • 8Burleigh M E,Babaev V R,Oates J A,et al.Cyclooxygenase-2 promotes early atherosclerotic lection formation in ApoE-deficient and C57BL/6 mice[J].J Mol Cell Cardiol,2005,39(3):443-52.
  • 9Chenevard R,Hurlimann D,Bechir M,et al.Selective COX-2 inhibition improves endothelial function in coronary artery disease[J].Circulation,2003,107(3):405-9.
  • 10Hsieh H L,Wu C B,Sun C C,et al.Sphingosine-1-phosphate induces COX-2 expression via PI3K/Akt and p42/p44 MAPK pathways in rat vascular smooth muscle cells[J].J Cell Physiol,2006,207(3):757-66.

二级参考文献30

  • 1Kojo H, Fukagawa M, Tajima K et al. Evaluation of human peroxisome proliferator-activated receptor (PPAR) subtype selectivity of a variety of anti-inflammatory drugs based on a novel assay for PPAR delta(beta) [ J ]. J Pharmacol Sci, 2003,93 ( 3 ) : 347 -55.
  • 2Wang Z, Breeher P. Salieylate inhibition of extracellular signal-regulated kinases and inducible nitric oxide synthase [ J ]. Hypertension, 1999, 34(6) :1259 -64.
  • 3Lagunas L, Bradbury CM, Laszlo A et al. Indomethacin and ibuprofen induce Hsc70 nuclear localization and activation of the heat shock response in HeLa cells[ J]. Biochem Biophys Res Commun,2004, 313(4) : 863 -70.
  • 4Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for the aspirin-like drugs [ J ]. Nature, 1971, 231 ( 25 ) :232 -5.
  • 5Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimers disease: Systematic review and meta-analysis of observational studies [ J ]. BMJ, 2003, 327(7407) : 128.
  • 6Baron JA, Sandler RS. Nonsteroidal anti-inflammatory drugs and cancer prevention[ J]. Annu Rev Med, 2000, 51 : 511 - 23.
  • 7Hinz B, Brune K. Cyclooxygenase-2-10 years later[J]. J Pharmacol Exp Ther, 2002, 300(2) :367 -75.
  • 8Steinmeyer J. Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs[ J]. Arthritis Res,2000, 2(5) : 379 -85.
  • 9Turini ME, du Bois RN. Cyclooxygenase-2: A therapeutic target[J]. Annu Rena Med,2002, 53:35 -57.
  • 10Awtry EH, Loscalzo J. Aspirin[ J]. Circulation ,2000. 101 (10) :1206 - 18.

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