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高尿酸血症损伤大鼠血管反应性
【机构】 重庆医科大学附属第一医院药剂科; 中国协和医科大学&中国医学科学院药物研究所;
【摘要】 目的:探讨高尿酸血症对大鼠肠系膜阻力血管的舒张和收缩反应的影响及机制。方法:以氧嗪酸连续给药28天建立大鼠高尿酸血症模型,采用离体肠系膜血管床灌流技术,观察血管床对氯化钾(KCl)和去甲肾上腺素(NE)的收缩反应、对乙酰胆碱(Ach)和硝普纳(SNP)的舒张剂反应性,同时检测血清NO、NOS、vWF含量和肠系膜血管CRP、eNOS、MCP-1蛋白表达情况。结果:氧嗪酸给药后两周,模型组血清尿酸水平比对照组显著增加,随造模时间延长,维持在较高水平;造模28天模型组大鼠血压比对照组有增加趋势,但差异无统计学意义;模型组离体肠系膜血管床对KCl和NE收缩反应比对照组增强,SNP和Ach对NE预收缩的血管床舒张反应比对照组减弱,但对Ach舒张反应减弱作用明显;模型组大鼠血清NO水平比对照组显著减少、血浆vWF水平显著升高、血清T-NOS活性显著降低、iNOS活性显著升高;模型组大鼠肠系膜血管CRP、MCP-1蛋白表达升高、eNOS蛋白表达降低。结论:高尿酸血症能导致大鼠肠系膜阻力血管内皮依赖性舒张功能受损和收缩反应增强,此异常血管反应可能与内皮炎性蛋白表达增加所致的内皮受损有关。
【Abstract】 Objective:To evaluate the effect of hyperuricacidemia on vascular relaxation and contraction response in mesenteric vascular bed in rats and its mechanism. Methods:Hyperuricemia model in rats was established by oxygen hydrochloride acid for 28 days continuous administration, isolated mesenteric vascular bed perfusion model were ex vivo established to observe the contractile response to potassium chloride (KCl) and norepinephrine (NE), and the vasodilator reactivity to acetylcholine (Ach) and sodium nitroprusside (SNP), while serum NO, NOS, vWF levels and the mesenteric vascular CRP, eNOS, MCP-1 protein expression in hyperuricemia rats were assayed. Results:Levels of serum uric acid in rats induced by oxonic acid were significantly inceased and blood pressure rised slightly compared with the control group. The perfused mesenteric vascular bed ex vivo of hyperuricacidemia rat had a sensitive contractile response to KCL and NE than the control group at various concentrations, and the perfused mesenteric vascular bed pre-constricted by NE showed weakened vasodilation response to SNP and Ach than the control group at various concentrations, but less effect on the relaxation response to Ach was observed. The NO level and T-NOS activity in serum and expression of eNOS protein in mesenteric vascular bed in hyperuricemia rat decreased significantly compared with the control group, and the vWF level in plasma, iNOS activity in serum, protein expression of CRP and MCP-1 in mesenteric vascular bed in hyperuricemia rat increased significantly. Conclusion:Hyperuricacidemia can lead to impaired endothelium-dependent relaxation and contraction response in rat mesenteric resistance vessels, this abnormal vascular reactivity is related to endothelial damage by endothelial inflammatory protein expression.
- 【会议录名称】 2010年中国药学大会暨第十届中国药师周论文集
- 【会议名称】2010年中国药学大会暨第十届中国药师周
- 【会议时间】2010-11
- 【会议地点】中国天津
- 【分类号】R589
- 【主办单位】中国药学会(Chinese Pharmaceutical Association)、天津市人民政府