K_(V)和K_(ATP)钾离子通道在尼古丁致小鼠肺动脉肌张力增强中的作用研究  

Effect of K_(V) and K_(ATP)channels in nicotine-induced enhancement of pulmonary artery tone in mice

作　　者：席迪 侯晓敏[2,3] 孙琳 赵旭[1,2] 董霖 张珂瑜 江雪露 施熠炜 秦小江[1,2] XI Di;HOU Xiao-min;SUN Lin;ZHAO Xu;DONG Lin;ZHANG Ke-yu;JIANG Xue-lu;SHI Yi-wei;QIN Xiao-jiang(School of Public Health,Shanxi Medical University,Taiyuan,Shanxi 030001,China;Institute of Environmental Exposure Vascular Diseases,Shanxi Medical University,Taiyuan,Shanxi 030001,China;College of Basic Medical Sciences,Shanxi Medical University,Taiyuan,Shanxi 030001,China;Department of Respiratory and Critical Care Medicine,The First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China)

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

出　　处：《毒理学杂志》2024年第4期251-256,共6页Journal of Toxicology

基　　金：国家自然科学基金面上项目(No.82373622);国家自然科学基金青年基金项目(No.82204042);国家卫生健康委员会尘肺病重点实验室开放课题(No.YKFKT006及NHC202307);山西省科技创新人才团队专项项目(No.202304051001038);山西省留学人员科技活动择优资助项目重点项目(No.20220019);山西省科技合作交流专项项目(No.202204041101022)。

摘　　要：目的研究4种钾离子通道在尼古丁致小鼠肺动脉肌张力增强中的作用。方法40只C57BL/6J小鼠,随机分为4组,空白对照组(自由饮水、摄食)、尼古丁低剂量组(0.02 mg/kg·d滴鼻)、尼古丁中剂量组(0.2 mg/kg·d滴鼻)和尼古丁高剂量组(2 mg/kg·d滴鼻),染毒8周。采用伊红-苏木素(HE)染色法检测各组小鼠肺动脉形态学改变;急性分离小鼠肺动脉,利用血管张力测定系统(DMT)及软件,测定各组小鼠肺动脉三级分支的内径;采用血管张力测定系统,检测尼古丁(10^(-11)~10^(-5)mol/L)对C57BL/6J小鼠肺动脉的收缩效果,以及血管收缩剂(KCl、PE、NE和AngII)对各组小鼠肺动脉的收缩程度;预孵4种钾通道抑制剂(K_(V)通道抑制剂4-AP、K_(Ca)通道抑制剂TEA、K_(ATP)通道抑制剂Gli和Kir通道抑制剂BaCl_(2)),检测其对尼古丁收缩肺动脉的影响。结果(1)HE染色结果显示,尼古丁干预后小鼠肺动脉管壁增厚,管腔狭窄,血管周围炎性组织浸润明显,且随尼古丁干预浓度增高,肺动脉重构程度增大;(2)随着尼古丁滴鼻浓度的增加,小鼠肺小动脉内径逐渐减小;(3)DMT离体血管张力检测结果显示,体外孵育尼古丁(10^(-11)~10^(-5)mol/L),可浓度依赖性地引起小鼠肺动脉收缩;(4)4种血管收缩剂(KCl,PE,NE和AngII)均能对小鼠肺动脉产生收缩效果;且随尼古丁滴鼻干预浓度的增加,肺动脉收缩程度逐渐增强;(5)预孵10^(-8)mol/L 4-AP和10^(-6)mol/L Gli后,尼古丁对肺动脉的收缩明显增强(F_(4-AP)=90.851,F_(Gli)=16.490,P<0.001),而预孵10^(-8)mol/L TEA和10^(-7)mol/L BaCl_(2)后,尼古丁对肺动脉的收缩增强无统计学意义。结论尼古丁染毒可致C57BL/6J小鼠肺动脉肌张力增高,其可能与K_(V)和K_(ATP)通道协同作用有关。Objective To investigate the role of four potassium ion channels in nicotine-induced augmentation of pulmonary artery tone in mice. Methods Forty C57BL/6J mice were randomly divided into four groups, control group(free water and food intake), nicotine low-dose group(0.02 mg/kg·d nose-drop), nicotine medium-dose group(0.2 mg/kg·d nose-drop), and nicotine high-dose group(2 mg/kg·d nose-drop) were infected with the drug for 8 weeks. Morphological changes of pulmonary arteries in each group were detected by HE staining. Pulmonary arteries of mice were acutely isolated, and the internal diameters of the tertiary branches of pulmonary arteries in each group were determined by using a wire myograph(DMT) and software. The constrictive effect of nicotine(10^(-11)~10^(-5) mol/L) on pulmonary arteries of C57BL/6J mice was examined by using a wire myograph and vascular constrictors(KCl, PE, NE, and AngII) on small pulmonary arteries in each group of mice. Four potassium channel inhibitors(K_(V) channel inhibitor 4-AP, K_(Ca) channel inhibitor TEA, K_(ATP) channel inhibitor Gli, and Kir channel inhibitor BaCl_(2)) were preincubated to detect their effects on the contraction of small pulmonary arteries by nicotine. Results(1) HE staining result showed that the wall of mouse pulmonary arteries was thickened, the lumen was narrowed, and perivascular inflammatory tissue infiltration was obvious after nicotine intervention, and the degree of remodeling of pulmonary arteries increased with increasing concentrations of nicotine intervention;(2) The internal diameter of small pulmonary arteries in mice decreased gradually with increasing concentrations of nicotine droplets.(3) The result of the DMT ex vivo vascular tone assay showed that in vitro incubation with nicotine(10^(-11)~10^(-5) mol/L), could concentration-dependently induce contraction of small pulmonary arteries in mice.(4) All four vasoconstrictors(KCl, PE, NE, and AngII) produced a contractile effect on pulmonary arteries in mice;and the degree of contraction of pulmo

关 键 词：尼古丁 肺动脉 肌张力 钾离子通道 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]