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酚酸類化合物對大鼠離體胸主動脈環(huán)舒張作用的相關(guān)研究

發(fā)布時間:2018-07-05 10:32

  本文選題:阿魏酸 + 咖啡酸; 參考:《河北醫(yī)科大學(xué)》2013年碩士論文


【摘要】:目的:觀察酚酸類化合物阿魏酸(FA)、咖啡酸(CA)、對香豆酸(p-CA)對大鼠離體胸主動脈環(huán)的舒張作用,并探討舒張血管環(huán)的作用機(jī)制及是否存在構(gòu)效關(guān)系。 方法:采用離體血管環(huán)灌流實驗,通過濃度累積加藥法,檢測阿魏酸(0.5-4mol/L)、咖啡酸(1-10mol/L)、對香豆酸(1-8mol/L)對去氧腎上腺素(PE)和氯化鉀(KCl)預(yù)收縮大鼠離體胸主動脈環(huán)的舒張作用,并觀察去內(nèi)皮或L-亞硝基精氨酸甲基酯(L-NAME)、亞甲藍(lán)(MB)、吲哚美辛(Indo)、格列苯脲(Gli)、四乙基胺(TEA)、維拉帕米(Verapamil)孵育后三種酚酸成分對PE預(yù)收縮血管的舒張作用的變化;并觀察在無鈣Krebs-henseleit (K-H)液中阿魏酸、咖啡酸、對香豆酸對PE和Ca~(2+)誘發(fā)動脈環(huán)收縮作用的影響。采用SPSS13.0分析軟件對數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)處理。 結(jié)果: 1阿魏酸、咖啡酸、對香豆酸具有濃度依賴性的舒張PE和KCl預(yù)收縮的大鼠離體胸主動環(huán)的作用。三者舒張PE預(yù)收縮血管的EC5(0mmol/L)分別為2.43±0.52、5.51±0.40、4.37±0.40,舒張KCl預(yù)收縮的EC5(0mmol/L)分別為2.17±0.15、5.53±0.38、4.37±0.57。三種酚酸成分舒張離體大鼠胸主動脈環(huán)作用的能力存在顯著性差異(P0.05),舒張能力從大到小依次為阿魏酸、對香豆酸、咖啡酸。 2阿魏酸在完整內(nèi)皮組和去內(nèi)皮組中的舒張作用的親和力指數(shù)pD2分別為2.62±0.08、2.60±0.03;咖啡酸分別為2.26±0.03、2.26±0.03;對香豆酸分別為2.36±0.04、2.36±0.03。三者在內(nèi)皮組和去內(nèi)皮組中的舒張大鼠胸主動脈環(huán)作用沒有統(tǒng)計學(xué)差異(P0.05)。 3加入一氧化氮合酶(NOS)阻斷劑L-NAME、環(huán)氧合酶(COX)阻斷劑吲哚美辛、鳥苷酸環(huán)化酶(GC)阻斷劑亞甲藍(lán)、鈣激活鉀通道(Kca)阻斷劑四乙基銨、ATP敏感性鉀通道(KATP)阻斷劑格列本脲后,沒有明顯的改變阿魏酸、咖啡酸、對香豆酸對大鼠離體胸主動脈環(huán)的舒張作用(P0.05)。 4在無鈣的K-H液中,阿魏酸、咖啡酸、對香豆酸可明顯抑制PE和Ca~(2+)誘發(fā)的依外Ca~(2+)性收縮反應(yīng)和依內(nèi)Ca~(2+)性收縮反應(yīng),而且隨著三者濃度的增加,這種抑制血管收縮的作用表現(xiàn)更明顯。三者抑制外鈣內(nèi)流和內(nèi)鈣釋放的能力中阿魏酸最強(qiáng),咖啡酸和對香豆酸無明顯差異。 結(jié)論: 1阿魏酸、咖啡酸、對香豆酸均有濃度依賴性的舒張離體大鼠胸主動脈環(huán)作用,且該舒張作用是非內(nèi)皮依賴的。 2阿魏酸、咖啡酸、對香豆酸舒張離體大鼠胸主動脈環(huán)作用的機(jī)制不是通過內(nèi)皮途徑和鉀通道途徑,而是直接作用在血管平滑肌上,通過抑制細(xì)胞外鈣內(nèi)流和細(xì)胞內(nèi)鈣釋放實現(xiàn)的。 3酚酸成分化學(xué)結(jié)構(gòu)中基團(tuán)(羥基和甲基)定位和數(shù)目的不同,使舒張血管作用存在差異,阿魏酸對香豆酸咖啡酸。
[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 鹵0.52 鹵0.402 鹵0.40 鹵4.37 鹵0.40 and 2.17 鹵0.155.53 鹵0.38 鹵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 鹵0.08, 2.60 鹵0.03, 2.26 鹵0.03 and 2.36 鹵0.04 鹵0.03 for caffeic acid, and 2.36 鹵0.04, 2.36 鹵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.
【學(xué)位授予單位】:河北醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2013
【分類號】:R151

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王桂芝;羅希鋒;孫博;侯云龍;李麗萍;鄭殿東;喬國芬;;,

本文編號:2099921


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