AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenz...AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle,aspirin (ASA) (a nonselective COX inhibitor),celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days.The area of colonic lesions,colonic blood flow (CBF),myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2,inducible form of nitric oxide synthase (iNOS),IL-1β and tumor necrosis factor (TNF)-α were assessed.The effects of glyceryl trinitrate (GTN),a NO donor,and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide,onopotassium salt (carboxy-PTIO),a NO scavenger,administered without and with ASA or NO-ASA,and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined.RESULTS:Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF,a significant rise in colonic weight,MPO activity and plasma IL-1β and TNF-α levels.These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)3-(trifluoromethyl)-1H-pyrazole (SC-560),but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E 2 (PGE 2) analog.Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO x content and CBF,suppression of MPO and downregulation of COX-2,iNOS,IL-1β and TNF-α mRNAs.Treatment with GTN,the NO donor,significantly inhibited the ASA-induced colonic lesions and increased CBF,while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF.These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals.CONCLUSION:NO-releasing ASA,in contrast to ASA,COX-1 inhibitors,and SC-560,accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.展开更多
目的应用外周动脉反应性充血指数(RHI)和血管内皮因子评估替格瑞洛对急性冠状动脉综合征(ACS)患者外周血管内皮功能的影响。方法选择ACS患者186例,随机分为对照组93例(氯吡格雷)和观察组93例(替格瑞洛),2组均常规口服阿司匹林等标准治疗...目的应用外周动脉反应性充血指数(RHI)和血管内皮因子评估替格瑞洛对急性冠状动脉综合征(ACS)患者外周血管内皮功能的影响。方法选择ACS患者186例,随机分为对照组93例(氯吡格雷)和观察组93例(替格瑞洛),2组均常规口服阿司匹林等标准治疗,应用Endo-外周动脉压力计无创内皮功能检测仪测定2组患者药物治疗后1、3及6个月的RHI,应用ELISA法检测相应时点血清内皮素1和NO水平,记录治疗期间不良反应的发生率。结果与治疗前比较,对照组和观察组治疗后3和6个月的RHI和NO水平升高、血清内皮素1降低(P<0.05);观察组治疗后6个月RHI高于对照组(1.65±0.34 vs 1.54±0.31,P=0.038);观察组治疗后3和6个月血清内皮素1和NO改善明显优于对照组(P<0.05)。2组均无致死性出血性事件发生,观察组与对照组轻微出血事件发生率比较,差异无统计学意义(3.2%vs 3.2%,P>0.05)。结论替格瑞洛有改善外周血管内皮依赖性舒张功能的作用,其可能对ACS患者的血管内皮功能有保护作用。展开更多
基金Supported by The financial grant K/PBW/000067 of the Polish Ministry of Science and Higher Education
文摘AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle,aspirin (ASA) (a nonselective COX inhibitor),celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days.The area of colonic lesions,colonic blood flow (CBF),myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2,inducible form of nitric oxide synthase (iNOS),IL-1β and tumor necrosis factor (TNF)-α were assessed.The effects of glyceryl trinitrate (GTN),a NO donor,and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide,onopotassium salt (carboxy-PTIO),a NO scavenger,administered without and with ASA or NO-ASA,and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined.RESULTS:Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF,a significant rise in colonic weight,MPO activity and plasma IL-1β and TNF-α levels.These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)3-(trifluoromethyl)-1H-pyrazole (SC-560),but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E 2 (PGE 2) analog.Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO x content and CBF,suppression of MPO and downregulation of COX-2,iNOS,IL-1β and TNF-α mRNAs.Treatment with GTN,the NO donor,significantly inhibited the ASA-induced colonic lesions and increased CBF,while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF.These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals.CONCLUSION:NO-releasing ASA,in contrast to ASA,COX-1 inhibitors,and SC-560,accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.
文摘目的应用外周动脉反应性充血指数(RHI)和血管内皮因子评估替格瑞洛对急性冠状动脉综合征(ACS)患者外周血管内皮功能的影响。方法选择ACS患者186例,随机分为对照组93例(氯吡格雷)和观察组93例(替格瑞洛),2组均常规口服阿司匹林等标准治疗,应用Endo-外周动脉压力计无创内皮功能检测仪测定2组患者药物治疗后1、3及6个月的RHI,应用ELISA法检测相应时点血清内皮素1和NO水平,记录治疗期间不良反应的发生率。结果与治疗前比较,对照组和观察组治疗后3和6个月的RHI和NO水平升高、血清内皮素1降低(P<0.05);观察组治疗后6个月RHI高于对照组(1.65±0.34 vs 1.54±0.31,P=0.038);观察组治疗后3和6个月血清内皮素1和NO改善明显优于对照组(P<0.05)。2组均无致死性出血性事件发生,观察组与对照组轻微出血事件发生率比较,差异无统计学意义(3.2%vs 3.2%,P>0.05)。结论替格瑞洛有改善外周血管内皮依赖性舒张功能的作用,其可能对ACS患者的血管内皮功能有保护作用。
