Astragaloside IV inhibits the development of heart failure in rats by regulating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway / 中华老年医学杂志

ABSTRACT

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.