中国动脉硬化杂志2017,Vol.25Issue(4):325-331,7.
氯膦酸二钠脂质体改善高血压小鼠血管内皮细胞功能及心肌肥厚
Clodronate liposome ameliorated endothelial function and cardiac hypertrophy in angiotensin Ⅱ hypertensive mice
摘要
Abstract
Aim To investigated the role and mechanism of macrophage in endothelial dysfunction and cardiac hypertrophy in AngⅡ-induced hypertensive mice.Methods C57BL/6 mice were randomly divided into four groups:normal +PBS group,normal+clodronate liposome (CL) group,Ang Ⅱ+PBS group,Ang Ⅱ+CL group.PBS or CL was injected via tail vein,and Ang Ⅱ was delivered by implantation of osmotic mini-pump.The systolic blood pressure (SBP) was measured by tail-cuff method,SBP was measured at 3 time points:at baseline,7 days and 14 days after AngⅡ infusion.HE staining was used to measure myocardial hypertrophy,endothelium dependent relaxation to acetylcholine in aortic rings was determined by organ chamber bath,the protein expression of p-eNOS,p-ERK1/2,TNF-α,IL-1β,TGF-β1,fibronectin was determined by Western blot.Results Compared with the normal+PBS mice,AngⅡ+PBS significantly increased systolic blood pressure (44%,P<0.05),macrophage infiltration in myocardial tissue (54%,P<0.05),heart weight (29%,P<0.05) as well as single myocardial cell area (48%,P<0.05),impaired acetylcholine-induced endothelium dependent relaxation (Emax-35%,P<0.05).The treatment with CL significantly reduced SBP (-25.28%,P<0.05),the area of single myocardial cell (-38.83%,P<0.05),and improve acetylcholine-induced endothelium dependent relaxation (Emax 12.63%,P<0.05) in Ang Ⅱ hypertensive mice.CL treatment also restored the expression of p-eNOS,p-ERK1/2,TNF-α,IL-1β,TGF-β1,fibronectin induced by AngⅡ (P<0.05).Conclusions The results demonstrate that CL protects against AngⅡ-induced endothelial dysfunction and myocardial damage and remodeling,the underlying mechanisms may involve reduction in myocardial macrophage infiltration and macrophage-derived cytokines.关键词
血管紧张素Ⅱ/高血压/心脏肥大/内皮细胞功能障碍/巨噬细胞Key words
Angiotensin Ⅱ/Hypertension/Cardiac hypertrophy/Endothelial dysfunction/Macrophage分类
医药卫生引用本文复制引用
刘彦彬,黄蕾,张英杰,林宇涵,周明生..氯膦酸二钠脂质体改善高血压小鼠血管内皮细胞功能及心肌肥厚[J].中国动脉硬化杂志,2017,25(4):325-331,7.基金项目
国家自然科学基金项目(81470532、81670384) (81470532、81670384)