解剖学杂志2023，Vol.46Issue(6)：468-475,8.DOI:10.3969/j.issn.1001-1633.2023.06.002
卡格列净改善自发性高血压大鼠主动脉重构的作用及其机制
Effects and mechanisms of Canagliflozin in mitigating aortic remodeling in spontaneously hypertensive rats
摘要
Abstract
Objective:To explore the effect of Canagliflozin on thoracic aorta remodeling in spontaneous hypertension rats(SHR)by regulating vascular smooth muscle cell proliferation,migration,and the renin-angiotensin-aldosterone system(RAAS)/transforming growth factor β1(TGF-β1)signaling pathway.Methods:The rats were divided into normal blood pressure control group(WKY group),SHR group,and SHR+Canagliflozin group.Tail-cuff sphygmomanometer was used to monitor the rats tail artery blood pressure(BP).H-E staining was used to evaluate the media thickness of thoracic aortic wall and the ratio of media thickness to lumen diameter.Masson staining was used to detect the degree of vascular wall fibrosis.Vascular smooth muscle cells(VSMCs)were isolated and cultured from thoracic aorta of WKY and SHR.Cells were divided into WKY group,WKY+ Canagliflozin group,SHR group,and SHR+Canagliflozin group.Scratch assay was conducted to evaluate cell migration,while CCK-8 assay was performed to assess cell proliferation.The expressions of alpha-smooth muscle actin(α-SMA),secreted phosphoprotein 1(SPP1),collagen typeⅠ alpha(Col1a),collagen type Ⅲ alpha(Col3a),angiotensinogen(AGT),angiotensin Ⅱ receptor 1(AGTR1)and TGF-β1 were detected by real-time quantitative polymerase chain reaction and Western blotting.Results:After eight weeks of canagliflozin administration,compared with the SHR group,the blood pressure,thoracic aortic media thickness,media thickness/lumen diameter ratio,and collagen deposition degree in the SHR+Canagliflozin group were decreased.The proliferation and migration ability of VSMCs in SHR group was significantly enhanced compared with that in WKY group,the expression of α-SMA was decreased,and the expression of SPP1,Col1a,Col3a,AGT,AGTR1 and TGF-β1 were increased.Compared with SHR group,SHR+Canagliflozin group significantly reduced the proliferation and migration capacity of VSMCs,and the expression of α-SMA was increased,and the expressions of SPP1,Colla,Col3a,AGT,AGTR1,and TGF-β1 were decreased.Conclusion:Canagliflozin may inhibit the proliferation and migration of hypertensive vascular smooth muscle cells by inhibiting RAAS/TGF-β1 signaling pathway,thereby improving aortic vascular remodeling in SHR.关键词
高血压/血管重构/血管平滑肌细胞/卡格列净/肾素-血管紧张素-醛固酮系统/转化生长因子β1Key words
hypertension/vascular remodeling/vascular smooth muscle cell/Canagliflozin/renin-angiotensin-aldosterone system/transforming growth factor β1引用本文复制引用
杨忠海,李爱花,高子雅,姚庆苹,符娟,严志强,刘化进..卡格列净改善自发性高血压大鼠主动脉重构的作用及其机制[J].解剖学杂志,2023,46(6):468-475,8.基金项目
国家自然科学基金(11772198) （11772198）
