杜鹃素对高盐膳食致冠状动脉重构的影响及机制  

Effect and mechanism of farrerol in coronary artery remodeling induced by high-salt diet

作　　者：秦小江[1] 杨晓宇 许欣荣 柴丽娜 郭耘莛 杜旭峰[2] 施熠炜[3] 侯晓敏[4] QIN Xiao-jiang;YANG Xiao-yu;XU Xin-rong;CHAI Li-na;GUO Yun-ting;DU Xu-feng;SHI Yi-wei;HOU Xiao-min(School of Public Health,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;Department of Sports Rehabilitation,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;Department of Respiratory and Critical Care Medicine,The First Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学公共卫生学院,山西太原030001 [2]山西医科大学运动康复系,山西太原030001 [3]山西医科大学第一医院呼吸与重症医学科,山西太原030001 [4]山西医科大学基础医学院,山西太原030001

出　　处：《中国临床药理学杂志》2022年第9期939-943,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(81803282);山西省基础研究计划自然科学研究面上项目基金资助项目(202103021224227);山西省归国留学基金资助项目(2020-086,2020-075,2020-167);山西省高校科技创新基金资助项目(2020L0193);细胞生理学教育部重点实验室(山西医科大学)开放基金资助项目(CPOF202117,CPOF202109)。

摘　　要：目的 研究杜鹃素通过调控ANO1改善高盐致冠状动脉重构的作用并探讨其机制。方法 将40只雄性C57BL/6J小鼠,随机分为空白对照组(正常饮食、摄食),高盐模型组(8%高盐饮食),低剂量杜鹃素组(8%高盐饮食+12.5 mg·kg^(-1)·d^(-1)杜鹃素),中剂量杜鹃素组(8%高盐饮食+25 mg·kg^(-1)·d^(-1)杜鹃素)和高剂量杜鹃素组(8%高盐饮食+50 mg·kg^(-1)·d^(-1)杜鹃素)。每组10只。用苏木精-伊红(HE)染色观察各组小鼠的冠状动脉形态学变化;用离体心脏灌流系统测定各组小鼠的冠状动脉流量;用微血管张力测定仪检测各组小鼠离体冠状动脉血管环的张力反应变化;用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹(Western blot)法测定各组小鼠冠状动脉组织ANO1的mRNA和蛋白表达水平;用全细胞膜片钳记录各组小鼠冠状动脉平滑肌细胞的钙激活氯离子通道(CaCC)电流。结果 HE染色结果显示,与空白对照组相比,高盐模型组小鼠冠状动脉出现明显的重构现象,杜鹃素可浓度依赖性改善其冠状动脉重构程度。空白对照组、高盐模型组和低、中、高剂量杜鹃素组的非肌化百分比分别为(60.13±3.12)%,(15.00±2.76)%,(19.35±3.11)%,(27.99±2.34)%和(50.16±3.45)%;部分肌化百分比分别为(23.07±2.57)%,(40.25±2.13)%,(26.21±2.09)%,(31.22±2.18)%和(37.35±3.26)%;完全肌化百分比分别为(15.89±2.32)%,(24.46±1.27)%,(17.05±1.48)%,(20.86±1.18)%和(22.27±1.62)%。与空白对照组相比,高盐模型组小鼠1 min冠状动脉流量显著减少;低、中、高剂量杜鹃素组小鼠冠状动脉流量逐渐增加。结论 杜鹃素可改善高盐所致的冠状动脉重构,其机制可能与其下调ANO1有关。Objective To study the effect and mechanism of farrerol down-regulating ANO1 to improve coronary artery remodeling induced by high salt. Methods Forty male C57 BL/6 J mice were randomly divided into five groups(10 mice each group): normal control group(normal diet, food intake), high-salt model group(8% high-salt diet), low-dose farrerol group(8% high-salt diet + 12.5 mg·kg^(-1)·d^(-1)farrerol), medium-dose farrerol group(8% high-salt diet+25 mg·kg^(-1)·d^(-1)farrerol) and high-dose farrerol group(8% high-salt diet +50 mg·kg^(-1)·d^(-1)farrerol).HE stainning were used to observe the morphological changes of the coronary arteries of mice;the isolated cardiac perfusion system were used to measure the coronary artery flow of mice;the microvascular tension meter were used to detect the tension of the isolated coronary ring;reserve transcription polymerase chain reaction( RT-PCR) and Western blot were used to determine the expression levels of ANO1 mRNA and protein in the coronary artery tissues;whole-cell patch clamp were used to record the CaCC currents of coronary artery smooth muscle cells. Results The results of HE stainning showed that compared with the normal control group,the coronary arteries of the mice in the high-salt model group showed obvious remodeling and farrerol could improve the degree of coronary artery remodeling in a dose-dependent manner. The non-muscularization percentages of the normal control group,high-salt model group,low-dose farrerol group, medium-dose farrerol group and high-dose farrerol group were( 60. 13 ± 3. 12) %,( 15. 00 ± 2. 76) %,( 19. 35 ± 3. 11) %,( 27. 99 ± 2. 34) % and( 50. 16 ± 3. 45) %;the partial muscularization percentages were( 23. 07 ± 2. 57) %,( 40. 25 ± 2. 13) %,( 26. 21 ± 2. 09) %,( 31. 22 ± 2. 18) % and( 37. 35 ± 3. 26) %;the complete muscularization percentages were( 15. 89 ± 2. 32) %,( 24. 46 ± 1. 27) %,( 17. 05 ± 1. 48) %,( 20. 86 ± 1. 18) % and( 22. 27 ± 1. 62) %. Compared with the normal control group,the one-minute coronary flow of mice in

关 键 词：杜鹃素 高盐膳食 冠状动脉重构 钙激活氯离子通道 

分 类 号：R28[医药卫生—中药学]