杜鹃素通过激活Kv通道舒张C57BL/6J小鼠离体肺动脉  

Farrerol relaxes isolated pulmonary arteries in C57BL/6J mice by activating Kv channel

作　　者：张珂瑜 侯晓敏[2,3] 邹佳佳 饶国娇 江雪露 董霖 施熠炜[5] 秦小江[1,2,4] ZHANG Keyu;HOU Xiaomin;ZOU Jiajia;RAO Guojiao;JIANG Xuelu;DONG Lin;SHI Yiwei;QIN Xiaojiang(Medical Science Academy;Environmental exposure vascular disease institute;Basic Medical College;School of Public Health,Shanxi Medical University;Department of Pulmonary and Critical Care Medicine,the First Hospital of Shanxi Medical University,Shanxi 030001,Taiyuan,China)

机构地区：[1]山西医科大学医学科学院 [2]山西医科大学环境暴露血管疾病研究所 [3]山西医科大学基础医学院 [4]山西医科大学公共卫生学院 [5]山西医科大学第一医院呼吸与危重症医学科,山西省太原市030001

出　　处：《中国动脉硬化杂志》2025年第3期202-208,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金面上项目(82373622);国家自然科学基金青年科学基金项目(82204042);国家卫生健康委员会尘肺病重点实验室开放课题(YKFKT006和NHC202307);山西省科技创新人才团队专项项目(202304051001038);山西省科技合作交流专项项目(202204041101022);山西省自然科学基金面上项目(202103021224227);山西省留学人员科技活动择优资助项目重点项目(20220019);山西医科大学2024年高等教育“百亿工程”科技引导专项—基础-临床双向转化专项(BYJL067)。

摘　　要：[目的]研究杜鹃素对C57BL/6J小鼠离体肺动脉的舒张作用及机制。[方法]麻醉小鼠,迅速取出肺组织置于4℃K-H缓冲液中,显微镜下分离得到肺动脉,并剪成长约2 mm的血管环备用。(1)杜鹃素对小鼠离体肺动脉静息张力的影响:选取具有活性的小鼠肺动脉环,在静息状态下加入不同浓度的杜鹃素(10^(-6)、3×10^(-6)、10^(-5)、3×10^(-5)及10^(-4) mol/L)。(2)杜鹃素舒张小鼠肺动脉实验:苯肾上腺素(PE,1μmol/L)或KCl(60 mmol/L)诱导小鼠肺动脉收缩达到平台期后,加入不同浓度的杜鹃素(10^(-6)、3×10^(-6)、10^(-5)、3×10^(-5)及10^(-4) mol/L)。(3)杜鹃素抑制肺动脉收缩实验:在加入或未加入杜鹃素的情况下,加入PE(10^(-9)、3×10^(-9)、10^(-8)、3×10^(-8)、10^(-7)、3×10^(-7)及10^(-6) mol/L)或KCl(20、30、40、60、80及120 mmol/L)诱导小鼠离体肺动脉收缩,并记录血管张力的变化。(4)无钙或复钙实验:在加入或未加入杜鹃素的情况下,记录小鼠离体肺动脉在无钙或复钙{2.5 mmol/L[Ca^(2+)]ex}状态下血管张力的变化。(5)杜鹃素舒张小鼠离体肺动脉与钾离子通道的关系:首先用60 mmol/L KCl溶液收缩小鼠肺动脉至平台期,随后分别加入3 mmol/L 4-氨基吡啶(4-AP)、2 mmol/L四乙胺(TEA)、30μmol/L BaCl_(2)和10μmol/L格列本脲(Gli)处理15 min,最后通过加入浓度梯度杜鹃素对肺动脉进行舒张。[结果]杜鹃素对静息状态下小鼠肺动脉张力无明显影响,但对PE和KCl诱导的小鼠肺动脉收缩具有浓度依赖性舒张作用;3×10^(-5) mol/L杜鹃素预处理显著降低PE和KCl诱导的小鼠肺动脉最大收缩(P<0.01),以及显著降低在无钙或复钙条件下KCl诱导的小鼠肺动脉收缩(P<0.01)。加入电压依赖性钾离子通道阻滞剂4-AP显著降低杜鹃素对小鼠肺动脉的最大舒张率(P<0.01),而加入大电导钙激活钾离子通道阻滞剂TEA、内向整流钾离子通道阻滞剂BaCl_(2)或ATP敏感钾离子通道阻滞剂Gli对杜鹃素Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4℃K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pulmonary artery rings were treated with different concentrations of farrerol(10^(-6),3×10^(-6),10^(-5),3×10^(-5) and 10^(-4) mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10^(-6),3×10^(-6),10^(-5),3×10^(-5) and 10^(-4) mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experiment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concentrations of PE(10^(-9),3×10^(-9),10^(-8),3×10^(-8),10^(-7),3×10^(-7) and 10^(-6) mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were measured in the state of calcium free or recalcification{2.5 mmol/L[Ca^(2+)]ex}.(5)The relationship between farrerol induced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tetraethylammonium(TEA),30μmol/L BaCl_(2),and 10μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-d

关 键 词：杜鹃素 肺动脉 舒张血管 钾离子通道 

分 类 号：R5[医药卫生—内科学] R363[医药卫生—临床医学]