RESUMEN
Objective:To investigate the protective effects and related mechanisms of Astragaloside Ⅳ(ASⅣ)alleviating Angiotensin II-induced cardiomyocyte hypertrophy.Methods:H9c2 cardiomyocytes were divided into six groups: normal control group, ASⅣ group(ASⅣ 100 μmol/L), AngⅡ group(AngⅡ 1 μmol/L), and three ASⅣ dose experiments(AngⅡ 1 μmol/L + ASⅣ 25 μmol/l group, AngⅡ 1 μmol/L+ ASⅣ 50 μmol/l group, AngⅡ1 μmol/L+ ASⅣ 100 μmol/L group), and simultaneously cultured for 24 hours.Cardiomyocyte viability was assessed by CCK8 assay, and surface area of culturedcardiomyocytes in each group was assessed by immunofluorescence assay.Atrial natriuretic peptide(ANP)mRNA expression was assessed by fluorescence real-time quantitative RT-PCR.And LC3 protein expression, an autophagy related protein, was assessed by Western blotting as well as immunofluorescence.Results:(1)AngⅡ decreased cardiomyocyte H9c2 viability in a dose-dependent manner( P<0.05). ASⅣ could inhibit the decrease of cardiomyocyte H9c2 viability in response to AngⅡ in a dose-dependent manner( P<0.05). (2)H9c2 cardiomyocytes induced by AngⅡ showed a significantly larger cell area and significantly higher ANP mRNA and ANP protein expression compared with controls.Different concentrations of ASⅣ intervention could reverse the increase of cardiomyocyte H9c2 area induced by AngⅡ and also decreased the expression of ANP protein induced by AngⅡ in a dose-dependent manner(all P<0.05). (3)Compared with the control group, the autophagy level and the expression of autophagy marker LC3II/I of H9c2 cardiomyocytes induced by AngⅡ were significantly increased(all P<0.05). ASⅣ could inhibit AngⅡ-activated autophagy, and the difference was statistically significant( P<0.05). ASⅣ inhibited the expression of LC3II/I in H9c2 cardiomyocytes stimulated by AngⅡ, and the difference was statistically significant( P<0.05). Conclusions:ASⅣ inhibits AngⅡ-induced cardiac hypertrophy by inhibiting autophagy of cardiomyocytes.
RESUMEN
Objective:To investigate the effect of Astragaloside Ⅳ on abdominal aorta constriction-induced cardiac hypertrophy by activating the nuclear factor E2-related factor 2/heme oxygenase-1(Nrf2/ HO-1)signaling pathway, so as to improve cardiac function.Methods:From Sep.2017 to Jan.2019, 40 male SD rats were selected and abdominal aortic constriction(AAC)was used to establish a rat model of chronic heart failure.Rats were divided into three ACC groups: the model group, the benazepril HCl group and the Astragaloside Ⅳ group, plus the sham operation group.Rats in the benazepril HCl and Astragaloside Ⅳ groups were given 10 mg·kg -1·d -1 benazepril HCl 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-diastolic 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.Compared 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)mm]and the BNP level[(99.40±4.97)mmol/L and(120.66±5.80)mmol/L]all decreased( P<0.05), but the mRNA expression of Nrf2(1.06±0.01 and 1.04±0.01)and HO-1(1.08±0.06 and 0.95±0.02)increased in the benazepril HCl and Astragaloside Ⅳ groups, respectively( P<0.01). Conclusions:Astragaloside Ⅳ has an effect of anti-oxidative stress, can inhibit heart failure and improve cardiac function, and its mechanisms may be related to the Nrf2/ HO-1 signaling pathway.