摘要
目的:探讨芹菜素通过调控窖蛋白-1(Caveolin-1)对慢性心力衰竭(CHF)大鼠血管紧张素 1-7(Ang1-7)及左室舒张功能的机制研究.方法:按照随机数字表法将大鼠分为假手术(Sham)组、CHF组、芹菜素组、Caveolin-1 组及联合组,每组 10 只,除 Sham组外均建立 CHF大鼠模型.建模后 24 h,芹菜素组大鼠腹腔注射 2 mg/kg的芹菜素,Caveolin-1 组腹腔注射 1.2 mg/kg的 Caveolin-1质粒的脂质体溶液,联合组大鼠腹腔注射 2 mg/kg的芹菜素及 1.2 mg/kg的 Caveolin-1 质粒的脂质体溶液,Sham组及 CHF组大鼠腹腔注射等体积生理盐水.比较各组大鼠心脏收缩及舒张功能指标、血清因子水平;苏木精-伊红(HE)染色检测心肌组织病理形态;电镜观察心房超微结构;免疫组化检测心肌组织血管生成情况;蛋白免疫印迹检测心肌组织Caveolin-1、缺氧诱导因子 1(HIF-1)、血管内皮生长因子(VEGF)蛋白水平.结果:CHF组与 Sham组比较,大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、Ang1-7及 Caveolin-1蛋白、HIF-1蛋白、VEGF蛋白降低,左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、肾素活性(PRA)升高,差异有统计学意义(P<0.05);芹菜素组、Caveolin-1组与 CHF组比较,大鼠 LVEF、LVFS、Ang1-7、Caveolin-1 蛋白、HIF-1 蛋白、VEGF蛋白及血管数目升高,LVESD、LVEDD、LVEDV、LVESV、AngⅡ、ALD、PRA降低,差异有统计学意义(P<0.05);芹菜素组与 Caveolin-1 组各指标比较,差异均无统计学意义(P>0.05);联合组与芹菜素组及 Caveolin-1组各指标比较,差异均有统计学意义(P<0.05).结论:芹菜素对慢性心力衰竭大鼠心脏舒张及收缩功能具有改善作用,并可通过上调 Ang1-7改善心肌重塑从而保护心脏,其机制可能与激活 Caveolin-1 表达而增加心肌新生血管相关.
Abstract
Objective:To investigate the effect of apigenin regulating Caveolin-1 on angiotensin 1-7(Ang1-7)and left ventricular diastolic function in rats with chronic heart failure.Methods:According to random number table method,the rats were divided into Sham group,chronic heart failure(CHF)group,apigenin group,Caveolin-1 group and combined group with 10 rats in each group.CHF rat models were established except Sham group.24 h after modeling,the apigenin group rats were intraperitoneally injected 2 mg/kg apigenin,Caveolin-1 group was intraperitoneally injected with 1.2 mg/kg liposome solution of Caveolin-1 plasmid,rats in the combined group were intraperitoneally injected with 2 mg/kg apigenin and 1.2 mg/kg liposome solution of Caveolin-1 plasmid,rats in Sham group and CHF group were intraperitoneally injected with equal volume of normal saline.Cardiac systolic and diastolic function indexes and serum factor levels were compared among all groups.Hematoxylin-eosin(HE)staining was used to detect the pathological morphology of myocardium.The ultrastructure of atrium was observed by electron microscope.Myocardial angiogenesis was detected by protein immunohistochemistry.The protein levels of hypoxia-inducing factor 1(HIF-1),Caveolin-1,vascular endothelial growth factor(VEGF)were detected by Western Blot.Results:Compared with Sham group,left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),Ang1-7,Caveolin-1,HIF-1,VEGF,and vascular number decreased in CHF group(P<0.05).Compared with Sham group,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),angiotensin Ⅱ(AngⅡ),aldosterone(ALD)and renin activity(PRA)increased in CHF group(P<0.05).Compared with CHF group,LVEF,LVFS,Ang1-7,Caveolin-1,HIF-1,VEGF,and the number of blood vessels in apigenin group and Caveolin-1 group increased,LVESD,LVEDD,LVEDV,LVESV,AngⅡ,ALD and PRA decreased(P<0.05).There were no significant differences between apigenin group and Caveolin-1 group(P>0.05).Compared with apigenin group,combined group and Caveolin-1 group,there were statistically significant differences in all indexes(P<0.05).Conclusion:Apigenin can improve cardiac diastolic and systolic functions in rats with chronic heart failure,and can improve myocardial remodeling and protect the heart by upregulating Ang1-7.The mechanism may be related to the activation of Caveolin-1 expression and the increase of myocardial angiogenesis.
维普
万方数据