乙酰异羟肟酸的舒张血管作用及其机制  

Vasodilating effect and mechanism of acetohydroxamic acid on isolated thoracic aorta of rats

作　　者：李发珍 谢童 范彦英[1] 杨彩红[1] LI Fa-zhen;XIE Tong;FAN Yan-ying;YANG Cai-hong(Department of Pharmacology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学药理学教研室,山西太原030001

出　　处：《中国药理学与毒理学杂志》2020年第6期418-427,共10页Chinese Journal of Pharmacology and Toxicology

基　　金：山西省自然科学基金(201901D111198);山西省“1331工程”重点学科建设计划基金(XK201708)。

摘　　要：目的研究乙酰异羟肟酸(AHA)降血压和舒张胸主动脉血管的作用及其机制。方法(1)动物实验:8周龄SD雄性大鼠,ip给予AHA 50和100 mg·kg^-1,每5 d给药1次,共5次。分别在给药前1 d、给药第13天和给药第26天测收缩压(SBP)和舒张压(DBP);HE染色观察大鼠胸主动脉血管组织形态变化。(2)离体实验:①累积浓度AHA(0.1,1,3,10,30和100μmol·L^-1)处理大鼠离体胸主动脉内皮完整血管环,检测血管环张力。②大鼠离体胸主动脉内皮完整和去内皮血管环用去甲肾上腺素(NE,1μmol·L^-1)和KCl(60 mmol·L^-1)预收缩,稳定后每10 min累积加入AHA(0.1,1,3,10,30和100μmol·L^-1),计算血管舒张百分比。③内皮完整血管环分为AHA组、AHA+左旋硝基精氨酸甲酯(L-NAME)组和AHA+吲哚美辛(Indo)组。L-NAME(0.1 mmol·L^-1)或Indo(0.01 mmol·L^-1)孵育30 min后,加NE(1μmol·L^-1)预收缩,血管收缩稳定后,累积加入AHA(0.1,1,3,10,30和100μmol·L^-1),计算累积浓度AHA舒张血管百分比。④内皮完整血管环分为AHA组、AHA+4-氨基吡啶(4-AP,1 mmol·L^-1)、AHA+格列苯脲(Gli,0.01 mmol·L^-1)、AHA+澳化四乙胺(TEA,1 mmol·L^-1)和AHA+BaCl2(0.1 mmol·L^-1)组。4-AP,Gli,TEA和BaCl2孵育30 min后,加NE(1μmol·L^-1)预收缩,血管收缩稳定后,累积加入AHA(0.1,1,3,10,30和100μmol·L^-1),计算累积浓度AHA血管舒张百分比。⑤内皮完整血管环分为AHA 1,10和100μmol·L^-1组,实验组分别加入不同浓度的AHA,预孵30 min后,加入累积浓度的CaCl2(0.1,0.3,1,3和10 mmol·L^-1),计算AHA各实验组血管收缩百分比。⑥内皮完整血管环分为AHA 1,10和100μmol·L^-1组,实验组分别加入不同浓度的AHA,预孵30 min后加入NE(1μmol·L^-1),计算AHA各实验组血管收缩张力。结果(1)动物实验:与正常对照组相比,AHA 50和100 mg·kg^-1组大鼠SBP和DBP均显著降低(P<0.01);HE染色未见AHA组大鼠胸主动脉组织形态明显改变。(2)离体实验:①累积浓度AHA对静息状态的大鼠胸主动脉内皮OBJECTIVE To investigate the effect of acetohydroxamic acid(AHA)on lowering blood pressure and relaxing the thoracic aorta.METHODS(1)Animal experiment:8-week-old SD male rats were randomly divided into normal control group(ip equal volume of saline),AHA 50 and 100 mg•kg-1.The drug was administered once every 5 d for a total of 5 times,and the systolic and diastolic blood pressure of the rats were measured with a non-invasive sphygmomanometer on the day before,the 13th and the 26th day of administration.The morphological changes of the thoracic aorta and blood vessels were observed by HE staining.(2)In vitro experiment:①The cumulative concentration of AHA(0.1,1,3,10,30 and 100μmol·L^-1)was used to treat the complete vascular ring of the isolated thoracic aorta endothelium in rats to detect the ring tension.②When the rat thoracic aortic ring with End+and End-was pre-contracted with norepinephrine(NE)1μmol·L^-1 and KCl 60 mmol·L^-1 for 10 minutes,AHA(0.1,1,3,10,30 and 100μmol·L^-1)and saline were cumulatively added into the organ bath.③The endothelium-intact(End+)vascular ring of the thoracic aorta was divided into the AHA group,AHA+L-NAME group and AHA+Indo group.After NG-nitro-L-arginine methyl ester(L-NAME)0.1 mmol·L^-1 or indomethacin(Indo)0.01 mmol·L^-1 was incubated for 30 min,NE(1μmol·L^-1)was added for pre-constriction.After the vasoconstriction was stabilized,AHA(0.1,1,3,10,30 and 100μmol·L^-1)was cumulatively added into the organ bath before the cumulative concentration of AHA was calculated as a percentage of diastolic blood vessels.④The endothelium-intact(End+)vascular ring of the thoracic aorta was divided into AHA group,AHA+4-AP group,AHA+Gli group,AHA+TEA group and AHA+BaCl2 group.After 4-aminopyridine(4-AP)1 mmol·L^-1,glibenclamide(Gli)0.01 mmol·L^-1,tetraethylammonium(TEA)1 mmol·L^-1 and barium chloride(BaCl2)1 mmol·L^-1 were incubated for 30 min,NE(1μmol·L^-1)was added to induce pre-constriction.After the vasoconstriction was stabilized,AHA(0.1,1,3,10,30 and 100μmol·L

关 键 词：乙酰异羟肟酸 胸主动脉 血管内皮 钙通道 

分 类 号：R972[医药卫生—药品]