摘要
[目的]探讨高盐摄入上调跨膜蛋白16A(TMEM16A)致小鼠冠状动脉重构的机制。[方法]36只8周龄雄性C57BL/6J小鼠随机分为3组:对照组(饮食中未额外添加NaCl)、10 g/L NaCl组(1 L纯水中含10 g NaCl)和20 g/L NaCl组(1 L纯水中含20 g NaCl),喂养8周。每周测量小鼠体重和收缩压(SBP);8周后,收集血清测量小鼠血清Na+浓度;测量小鼠左心室质量指数(LVMI)以评估高盐对小鼠心脏的影响;Langendorff逆行恒压灌流法测定小鼠冠状动脉流量(CF);HE染色评估小鼠冠状动脉形态学改变,并计算管壁厚度百分比及管壁面积百分比;微血管张力记录仪检测小鼠离体冠状动脉收缩性变化,以冠状动脉血管环面积标化其张力;Western blot检测小鼠冠状动脉中TMEM16A蛋白表达;免疫荧光双染检测小鼠冠状动脉中TMEM16A和α-平滑肌肌动蛋白(α-SMA)表达。[结果]8周后,10 g/L NaCl组和20 g/L NaCl组小鼠体重变化率均低于对照组,SBP均显著高于对照组(P<0.05或P<0.01)。与对照组相比,10 g/L NaCl组和20 g/L NaCl组小鼠血清Na+浓度均增加(P<0.05或P<0.01);高盐摄入可增加小鼠LVMI,降低小鼠CF,且均以20 g/L NaCl组小鼠最显著(P<0.01);10 g/L NaCl组和20 g/L NaCl组小鼠冠状动脉的管壁厚度百分比和管壁面积百分比均显著增加(均P<0.01);10 g/L NaCl组和20g/L NaCl组小鼠冠状动脉对60 mmol/L KCl和0.03μmol/L内皮素1的收缩反应均显著增强(P<0.01);20 g/L NaCl组小鼠冠状动脉中TMEM16A蛋白表达显著增加(P<0.01),10 g/L NaCl组和20 g/L NaCl组小鼠冠状动脉中TMEM16A和α-SMA荧光表达均显著增加(均P<0.01),且TMEM16A与α-SMA在冠状动脉中存在显著共定位。[结论]高盐摄入可致小鼠冠状动脉重构,其机制可能与上调冠状动脉TMEM16A的表达有关。
Aim To investigate the mechanism by which high-salt intake upregulates transmembrane protein 16A(TMEM16A)and induces coronary artery remodeling in mice.Methods Thirty-six 8-week-old male C57BL/6J mice were randomly divided into three groups:control group(no additional NaCl in the diet),10 g/L NaCl group(1 L of pure water contains 10 g of NaCl),and 20 g/L NaCl group(1 L of pure water contains 20 g of NaCl).Mice were fed for 8 weeks.Mouse body weight and systolic blood pressure(SBP)were measured weekly.After 8 weeks,serum was collected to measure serum Na+concentrations in mice;left ventricular mass index(LVMI)was measured to assess the effects of high-salt intake on the mouse heart;coronary flow(CF)was determined using the Langendorff retrograde constant-pressure perfusion method;HE staining was used to assess morphological changes in the coronary arteries,and calculate wall thickness(WT)percentage and wall area(WA)percentage.Microvascular tension recording instruments were employed to measure contractile changes in isolated coronary arteries from each group,standardizing coronary artery tension based on the area of the vascular ring.Western blot was used to detect TMEM16A protein expression in mouse coronary arteries.Dual immunofluorescence staining was used to detect TMEM16A andα-SMA expression in mouse coronary arteries.Results After 8 weeks,mice in the 10 g/L NaCl group and 20 g/L NaCl group showed a lower body weight change rate than control group,and SBP was significantly higher in both salt groups(P<0.05 or P<0.01).Compared with control mice,serum Na+concentration was increased in the 10 g/L NaCl group and 20 g/L NaCl group(P<0.05 or P<0.01).High-salt intake elevated LVMI and reduced CF,with the 20 g/L NaCl group exhibiting the most pronounced changes(P<0.01).Percent wall thickness and percent wall area of coronary arteries were significantly greater in both salt groups(all P<0.01).Contractile responses to 60 mmol/L KCl and 0.03μmol/L endothelin-1 in coronary arteries were significantly enhanced in the 10 g/L and 20 g/L NaCl groups(P<0.01).TMEM16A protein expression in coronary arteries was markedly up-regulated in the 20 g/L NaCl group(P<0.01),and immunofluorescence revealed significantly increased TMEM16A andα-SMA signals in both salt groups(all P<0.01).In addition,there was an obvious co-localization between TMEM16A andα-SMA.Conclusion High-salt intake causes coronary artery remodeling in mice,and its mechanism may be related to increasing TMEM16A expression.
作者
满志
秦小江
郑志发
方梦薇
孟欣
郭苏
张学凤
杨灵波
施熠炜
张明升
侯晓敏
MAN Zhi;QIN Xiaojiang;ZHENG Zhifa;FANG Mengwei;MENG Xin;GUO Su;ZHANG Xuefeng;YANGLingbo;SHI Yiwei;ZHANG Mingsheng;HOU Xiaomin(Medical Science Academy,Shanxi Medical University,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China;School of Public Health,Shanxi Medical University,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China;Department of Cardiovascular Surgery,Shanxi Bethune Hospital,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China;Basic Medical College,Shanxi Medical University,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China;Medical Insurance Office,Shanxi Bethune Hospital,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China;Department of Pulmonary and Critical Care Medicine,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China)
出处
《中国动脉硬化杂志》
2026年第2期103-110,共8页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金青年基金项目(82204042)
国家自然科学基金面上项目(82373622)
山西省科技创新人才团队(青年)项目(202304051001038)
山西省科技合作交流专项项目(区域合作项目)(202204041101022)
国家卫生健康委员会尘肺病重点实验室开放课题(NHC202307)
山西省高等教育“百亿工程”科技引导专项项目(BYJL067)
山西白求恩医院临床重点专科项目
山西省科技厅自由探索类青年项目(202203021222345)。
关键词
高盐摄入
跨膜蛋白16A
冠状动脉
血管重构
high-salt intake
transmembrane protein 16A
coronary artery
vascular remodeling
