摘要
目的探讨黄芪甲苷通过激活核因子E2相关因子2/血红素氧合酶-1(Nrf2/HO-1)信号通路抑制大鼠腹主动脉缩窄所致心力衰竭,改善大鼠心功能。方法2017年9月至2019年1月选取SD雄性大鼠40只,采用腹主动脉缩窄法(AAC)建立大鼠慢性心力衰竭模型,分为三组:模型组、贝那普利组、黄芪甲苷组,另外建立假手术组。贝那普利组和黄芪甲苷组分别给与10 mg·kg-1·d-1的贝那普利和50 mg·kg-1·d-1的黄芪甲苷灌胃,假手术组及模型组给与相同体积的生理盐水灌胃。8周后通过心脏彩超及血流动力学检测大鼠心脏结构及功能参数,免疫荧光法检测大鼠心肌细胞形态学变化,ELISA法检测大鼠血清中BNP水平变化,RT-qPCR检测大鼠心肌组织中Nrf2、HO-1 mRNA的表达情况。结果与假手术组相比,模型组大鼠的心脏股骨颈比(495.47±12.38)、心脏体重比(6.44±0.18)、左室舒张末期内径(4.72±0.04)mm、左室后壁舒张期厚度(1.87±0.03)mm、B型钠尿肽(BNP)含量(151.61±5.67)mmol/L均增高,Nrf2(0.36±0.02)及HO-1 mRNA(0.27±0.02)较假手术组均下降。与模型组相比,贝那普利组心脏股骨颈比(261.88±12.97)、心脏体重比(3.38±0.13)、左室舒张末期内径(5.84±0.05)mm、左室后壁舒张期厚度(1.57±0.03)mm、BNP(99.40±4.97)mmol/L降低,黄芪甲苷组心脏股骨颈比(286.40±12.56)、心脏体重比(3.71±0.15)、左室舒张末期内径(6.01±0.10)mm、左室后壁舒张期厚度(1.64±0.03)mm、BNP含量(120.66±5.80)mmol/L,较模型组均降低,贝那普利组Nrf2 mRNA水平(1.06±0.01)、HO-1 mRNA(1.08±0.06)与黄芪甲苷组Nrf2mRNA(1.04±0.01)、HO-1 mRNA(0.95±0.02)表达均增高(P<0.01)。结论黄芪甲苷具有抗氧化应激作用,可抑制心力衰竭,改善心功能,其机制可能与Nrf2/HO-1信号通路有关。
Objective To investigate the effect of Astragaloside IV on abdominal aorta constriction-induced cardiac hypertrophy by activating the nuclear factor E2-related factor 2/hem e oxygenase-1(Nrf2/HO-l)signaling pathway,so as to improve cardiac function.Methods From Sep.2017 to Jan.2019,40 male SD rats were vselected and abdominal aortic constriction(AAC)was used to establish a rat model of chronic heart failure.Rats were divided into three ACC group s:the model groups the benazepril HC1 group and the AstragalosideⅥgroup,plus the sham operation group.Rats in the benazepril HCI and Astragaloside IV groups were given 10 mg.kg-1·d-1 benazepril HCI and 50mg·kg-1·d-1 Astragaloside IV respectively by gavage,and the sham operation group and the model group were given normal saline of the same volume by gavage.After 8 weeks of treatment,cardiac structure and functional parameters were examined using cardiac color doppler ultrasound,while hemodynamics and morphological changes of myocardial cells were detected by immunofluorescence,serum brain natriuretic peptide(BNP)levels were detected by an enzyme linked immunosorbent assay(ELISA),and Nrf2 and HO-1 mRNA expression in myocardial tissues were detected by reverse transcription-quantitative real-time PCR(RT-qPCR).Results Compared with the sham operation group,the ratio of heart weight to femoral neck length(495.47±12.38),the ratio of heart weight to body weight(6.44±0.18),left ventricular end-diastolie diameter(LVEDD)(4.72±0.04 mm),left ventricular posterior wall thickness(LVPWT)(1.87±0.03)mm and the BNP level(151.61±5.67)mmol/L all increased(P<0.05),but the expression of mRNA Nrf2(0.36±0.02)and HO-1(0.27±0.02)decreased(P<0.01)in the model group.Com pared with the model group,the ratio of heart weight to femoral neck length(261.88±12.97 and 286.40±12.56),the ratio of heart weight to body weight(3.38±0.13 and 3.71±0.15),left ventricular end diastolic diameter(5.84±0.05)mm and(6.01±0.10)mm,left ventricular posterior wall thickness[(1.57±0.03)mm and(1.64±0.03)m
作者
宋秉春
孟凡静
聂佩
尉希清
张金国
Song Bingchun;Meng Fanjing;Nie Pei;Wei Xiqing;Zhang Jinguo(Deparment of Cardiology.the Affiliated Hospital of Jining Medical University.Jining 272029,China;Department of Geriatrics,the First People's Hospial of Jining,Jining 272000,China;Department of Cardiology,New Hospital District,Anqing Municipal Hos pital,Anqing 246000,China)
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2020年第9期1072-1076,共5页
Chinese Journal of Geriatrics
基金
山东省中医药科技发展计划项目(No.2017-277)
济宁医学院国家自然科学基金培育基金(No.JYP201733)
济宁市重点研发计划项目(No.2018SMNS006)。
关键词
黄芪甲苷
心力衰竭
氧合酶类
Astragaloside IV
Heart failure
Oxygenases
