摘要
目的观察虾青素灌胃对压力负荷导致小鼠左心室心肌肥厚的抑制作用,并探讨其机制。方法将24只雄性C57BL/6野生型小鼠随机分为假手术组、假手术+虾青素组、心肌肥厚组、心肌肥厚+虾青素组,每组6只。心肌肥厚组、心肌肥厚+虾青素组均采用胸主动脉缩窄术诱导建立压力负荷导致左心室心肌肥厚小鼠模型,假手术组、假手术+虾青素组不结扎胸主动脉;术后第1天,假手术+虾青素组和心肌肥厚+虾青素组每日给予虾青素150 mg/kg灌胃,假手术组和心肌肥厚组给予等体积生理盐水灌胃,持续4周。处死后称取并计算小鼠心脏质量与体质量比值(HW/BW)、心脏质量与胫骨长度比值(HW/TL);取各组小鼠心肌组织,HE和天狼猩红染色后观察肥厚和纤维化情况,计算心肌细胞横截面积和胶原容积分数,实时荧光定量PCR法检测心房利尿钠肽(ANP)、心肌β异构体(β-MHC)、Ⅰ型胶原纤维(Collα1)、结缔组织生长因子(CTGF)mRNA表达,羟胺法检测超氧化物歧化酶(SOD)活性,硫代巴比妥酸法检测丙二醛(MDA)含量,Western blotting法检测细胞核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)蛋白表达。结果假手术组及假手术+虾青素组小鼠心肌结构排列整齐,无明显纤维化;心肌肥厚组和心肌肥厚+虾青素组小鼠心脏体积增大、纤维化程度明显,且心肌肥厚组变化更明显。与假手术组及假手术+虾青素组比较,心肌肥厚组、心肌肥厚+虾青素组小鼠HW/BW、HW/TL、心肌细胞横截面积、胶原容积分数均升高,心肌组织ANP、β-MHC、Collα1、CTGF mRNA相对表达量及MDA表达均升高,心肌组织Nrf2、HO-1蛋白相对表达量、SOD活性均降低,且心肌肥厚组变化更明显(P均<0.05)。结论虾青素可减轻压力负荷导致的小鼠左心室心肌肥厚,其机制可能与激活Nrf2/HO-1信号通路而减轻心肌组织氧化应激反应有关。
Objective To investigate the inhibitory effects of astaxanthin(AST)on pressure overload-induced left ventricular hypertrophy in mice and to explore its molecular mechanism.Methods Twenty-four C57BL/6 wild-type male mice were randomly divided into the following four groups:sham group,sham+AST group,cardiac hypertrophy group,and cardiac hypertrophy+AST group,with 6 in each group.The model of left ventricular myocardial hypertrophy was established by thoracic aorta coarctation(TAC)in the cardiac hypertrophy group and cardiac hypertrophy+AST group.The thoracic aortas of mice in both the sham group and sham+AST group were not ligated.AST[150 mg/(kg·d)]was intragastrically administered daily from the next day after surgery for 4 weeks in sham+AST group and cardiac hyper⁃trophy+AST group.The mice in sham group and cardiac hypertrophy group were given the same volume of normal saline.After sacrifice,the ratios of heart weight/body weight(HW/BW)and heart weight/tibia length(HW/TL)of mice were measured.The hypertrophy and fibrosis degree of myocardium in mice were observed by HE staining and Picro Sirius Red(PSR)staining,and the cardiomyocyte cross-sectional area and collagen volume fraction were calculated.The mRNA ex⁃pression levels of atrial natriuretic peptide(ANP),myocardialβisoform(β-MHC),fibrosis-related molecules collagen fi⁃ber typeⅠ(Collα1),and connective tissue growth factor(CTGF)were detected by real-time PCR(RT-PCR).The activi⁃ty of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in myocardium were estimated by hydroxyl⁃amine method and thiobarbituric acid method,respectively.The protein expression levels of nuclear factor erythroid-de⁃rived 2-like 2(Nrf2)and Heme oxygenase 1(HO-1)were detected by Western blotting.Results The myocardial struc⁃tures in the sham group and sham+AST group were neatly arranged without fibrosis.In contrast,the heart volume and fi⁃brosis significantly increased in the cardiac hypertrophy group and cardiac hypertrophy+AST group,and the changes in
作者
向梅
许蓓
王晓玲
张利芸
XIANG Mei;XU Bei;WANG Xiaoling;ZHANG Liyun(Department of Cardiology,The Central Hospital of Wuhan,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430014,China)
出处
《山东医药》
CAS
2024年第23期47-51,共5页
Shandong Medical Journal
基金
湖北省武汉市卫健委医学科研项目(WX21Q01)。
