酚酸类化合物对大鼠离体胸主动脉环舒张作用的相关研究

发布时间：2018-07-05 10:32

本文选题：阿魏酸 + 咖啡酸　；参考：《河北医科大学》2013年硕士论文

【摘要】：目的：观察酚酸类化合物阿魏酸（FA）、咖啡酸（CA）、对香豆酸（p-CA）对大鼠离体胸主动脉环的舒张作用，并探讨舒张血管环的作用机制及是否存在构效关系。方法：采用离体血管环灌流实验，通过浓度累积加药法，检测阿魏酸(0.5-4mol/L)、咖啡酸(1-10mol/L)、对香豆酸(1-8mol/L)对去氧肾上腺素（PE）和氯化钾（KCl）预收缩大鼠离体胸主动脉环的舒张作用，并观察去内皮或L-亚硝基精氨酸甲基酯（L-NAME）、亚甲蓝（MB）、吲哚美辛（Indo）、格列苯脲（Gli）、四乙基胺（TEA）、维拉帕米（Verapamil）孵育后三种酚酸成分对PE预收缩血管的舒张作用的变化；并观察在无钙Krebs-henseleit （K-H）液中阿魏酸、咖啡酸、对香豆酸对PE和Ca~(2+)诱发动脉环收缩作用的影响。采用SPSS13.0分析软件对数据进行统计学处理。结果： 1阿魏酸、咖啡酸、对香豆酸具有浓度依赖性的舒张PE和KCl预收缩的大鼠离体胸主动环的作用。三者舒张PE预收缩血管的EC5（0mmol/L）分别为2.43±0.52、5.51±0.40、4.37±0.40，舒张KCl预收缩的EC5（0mmol/L）分别为2.17±0.15、5.53±0.38、4.37±0.57。三种酚酸成分舒张离体大鼠胸主动脉环作用的能力存在显著性差异（P0.05），舒张能力从大到小依次为阿魏酸、对香豆酸、咖啡酸。 2阿魏酸在完整内皮组和去内皮组中的舒张作用的亲和力指数pD2分别为2.62±0.08、2.60±0.03；咖啡酸分别为2.26±0.03、2.26±0.03；对香豆酸分别为2.36±0.04、2.36±0.03。三者在内皮组和去内皮组中的舒张大鼠胸主动脉环作用没有统计学差异（P0.05）。 3加入一氧化氮合酶（NOS）阻断剂L-NAME、环氧合酶(COX)阻断剂吲哚美辛、鸟苷酸环化酶(GC)阻断剂亚甲蓝、钙激活钾通道(Kca)阻断剂四乙基铵、ATP敏感性钾通道(KATP)阻断剂格列本脲后，没有明显的改变阿魏酸、咖啡酸、对香豆酸对大鼠离体胸主动脉环的舒张作用（P0.05）。 4在无钙的K-H液中，阿魏酸、咖啡酸、对香豆酸可明显抑制PE和Ca~(2+)诱发的依外Ca~(2+)性收缩反应和依内Ca~(2+)性收缩反应，而且随着三者浓度的增加，这种抑制血管收缩的作用表现更明显。三者抑制外钙内流和内钙释放的能力中阿魏酸最强，咖啡酸和对香豆酸无明显差异。结论： 1阿魏酸、咖啡酸、对香豆酸均有浓度依赖性的舒张离体大鼠胸主动脉环作用，且该舒张作用是非内皮依赖的。 2阿魏酸、咖啡酸、对香豆酸舒张离体大鼠胸主动脉环作用的机制不是通过内皮途径和钾通道途径，而是直接作用在血管平滑肌上，通过抑制细胞外钙内流和细胞内钙释放实现的。 3酚酸成分化学结构中基团（羟基和甲基）定位和数目的不同，使舒张血管作用存在差异，阿魏酸对香豆酸咖啡酸。
[Abstract]:Aim: to investigate the relaxation effect of phenolic acid compounds ferulic acid (FA), caffeic acid (CA) and coumaric acid (p-CA) on isolated thoracic aortic rings in rats, and to explore the mechanism of vasodilation and whether there is a structure-activity relationship. Methods: the effects of ferulic acid (0.5-4 mol / L), caffeic acid (1-10 mol / L) and coumaric acid (1-8 mol / L) on the relaxation of isolated rat thoracic aortic rings were measured by the method of concentration accumulation and administration of isolated vascular rings in vitro, and the effects of ferulic acid (0.5-4 mol / L), caffeic acid (1-10 mol / L) and coumaric acid (1-8 mol / L) on deoxyadrenaline (PE) and potassium chloride (KCl) precontractile thoracic aortic rings were measured. The vasodilation effects of three phenolic acid components on precontracted PE were observed after incubation with endothelium or L-NAME, methylene blue (MB), indomethacin (Indo), glibenclamide (Gli), tetraethylamine (tea) and verapamil. The effects of ferulic acid, caffeic acid and coumaric acid on the contraction of arterial rings induced by PE and Ca2 in calcium free Krebs-henseleit (K-H) solution were observed. SPSS 13.0 analysis software was used to process the data statistically. Results: 1Ferulic acid, caffeic acid, and coumaric acid had concentration-dependent relaxation of PE and KCl precontractile active rings in isolated rat thorax. The values of EC5 (0 mmol / L) of PE precontracted vessels were 2.43 卤0.52 卤0.402 卤0.40 卤4.37 卤0.40 and 2.17 卤0.155.53 卤0.38 卤0.57 of EC5 (0 mmol / L), respectively. There was significant difference in the relaxation ability of three phenolic acids in isolated rat thoracic aortic rings (P0.05). The diastolic ability was ferulic acid and coumaric acid in turn from large to small. The affinity index (pD2) of caffeic acid in intact endothelial group and deendothelium-free group was 2.62 卤0.08, 2.60 卤0.03, 2.26 卤0.03 and 2.36 卤0.04 卤0.03 for caffeic acid, and 2.36 卤0.04, 2.36 卤0.03 for coumaric acid, respectively. There was no significant difference between the three groups (P0.05). 3 adding nitric oxide synthase (NOS) blocker L-NAME, cyclooxygenase (Cox) blocker indomethacin, guanosine cyclase (GC) blocker methylene blue, and so on. Calcium activated potassium channel (KCA) blocker tetraethylammonium triphosphate ATP-sensitive potassium channel (K ATP) blocker glibenclamide did not significantly change ferulic acid, caffeic acid. Effects of coumaric acid on relaxation of isolated rat thoracic aortic rings (P0.05). 4 Ferulic acid, caffeic acid and p-coumaric acid could significantly inhibit Ca ~ (2) contraction induced by PE and Ca ~ (2) -induced contraction in Ca ~ (2). And with the increase of the concentration of the three, the inhibition of vasoconstriction is more obvious. Among them, ferulic acid was the strongest, while caffeic acid and p-coumaric acid had no significant difference. Conclusion: 1 Ferulic acid, caffeic acid, coumaric acid have concentration-dependent relaxation of isolated rat thoracic aortic rings, and the relaxation effect is endothelium-dependent. 2 Ferulic acid and caffeic acid. The mechanism of vasodilation of isolated rat thoracic aortic rings by coumaric acid is not through endothelial pathway and potassium channel pathway, but directly on vascular smooth muscle. By inhibiting extracellular calcium influx and intracellular calcium release, the location and number of groups (hydroxyl and methyl) in the chemical structure of phenolic acid were different, and the vasodilation effect of ferulic acid on coumaric acid was different.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R151

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