Astragaloside Ⅳ alleviating chronic intermittent hypoxia-induced cardiac injury by enhancing autophagy

QIN Lu-Yun; LUO Li-Fei; GUAN Peng; SUN Zhi-Min; WANG Na

doi:10.16098/j.issn.0529-1356.2021.02.017

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Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (2) : 270-276. DOI: 10.16098/j.issn.0529-1356.2021.02.017

Histology,Embryology and Developmental Biology

Astragaloside Ⅳ alleviating chronic intermittent hypoxia-induced cardiac injury by enhancing autophagy

QIN Lu-yun LUO Li-fei GUAN Peng SUN Zhi-min WANG Na*

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Abstract

Objective To investigate the protective effects of astragaloside Ⅳ（ASⅣ）on chronic intermittent hypoxia (CIH)-induced cardiac injury. Methods Twenty-four male adult Sprague Dawley rats were randomly assigned to control, CIH, CIH+ASⅣ, and ASⅣ group, 6 rats in each group. Circular nitrogen and oxygen were filled to make oxygen concentration change between 9%-21% for the CIH treated rats. The exposure cycle was repeated every 3 minutes, 8 hours/day for 35 days. ASⅣ was given by intragastric administration daily before intermittent hypoxia exposure in the CIH+ASⅣ group and ASⅣ group. The control group and CIH group were given normal saline of the same quantity. Echocardiography was used to analyse cardiac function. Myocardial structure was assessed by HE and wheat germ agglutinin staining. The apoptosis of cardiomyocytes was detected by TUNEL assay. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in heart were detected by commercial kits. Western blotting was used to evaluate the levels of Bcl-2, Bax, LC3, Beclin1, P62, and mammalian target of rapamycin（mTOR）. Results In the CIH group, the left ventricular ejection fraction (LVEF) and left ventricular internal diameter at end-systole (LVIDs) were inhibited, the myocyte cells showed disordered arranged, enlarged diameters and higher apoptosis rate. The MDA content was significantly elevated and the SOD activity decreased in CIH group when compared with those of control. What’s more, the expression level of Beclin 1 decreased while the P62 expression and the p-mTOR/mTOR ratio increased in the CIH group. Compared with the model group, the LVEF, LVIDs, SOD activity, LC3Ⅱ/Ⅰ ratio, and Beclin1 expression of rats in the CIH+ASⅣ group increased. The cardiomyocytes in the rats of CIH+ASⅣ group showed normal arrangement and diameters. The apoptosis rate, MDA content, P62 expression and the p-mTOR/mTOR ratio decreased in the CIH+ASⅣ group when compared with the CIH group. Conclusion ASⅣ can alleviate CIH-induced cardiac injury by promoting autophagy via mTOR.

Key words

Astragaloside Ⅳ / Chronic intermittent hypoxia / Hypertrophy / Autophagy / Mammalian target of rapamycin / Western blotting / Rat

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QIN Lu-yun LUO Li-fei GUAN Peng SUN Zhi-min WANG Na. Astragaloside Ⅳ alleviating chronic intermittent hypoxia-induced cardiac injury by enhancing autophagy[J]. Acta Anatomica Sinica. 2021, 52(2): 270-276 https://doi.org/10.16098/j.issn.0529-1356.2021.02.017

References

［1］ Sanchez-de-la-Torre M, Campos-Rodriguez F，Barbe F. Obstructive sleep apnoea and cardiovascular disease［J］. Lancet Respir Med, 2013, 1(1): 61-72.

［2］ Peppard PE, Young T, Barnet JH, et al. Increased prevalence of sleep-disordered breathing in adults［J］. Am J Epidemiol, 2013, 177(9): 1006-1014.

［3］ Sekizuka H, Osada N，Akashi YJ. Impact of obstructive sleep apnea and hypertension on left ventricular hypertrophy in Japanese patients［J］. Hypertens Res, 2017, 40(5): 477-482.

［4］ Patil SP, Ayappa IA, Caples SM, et al. Treatment of adult obstructive sleep apnea with positive airway pressure: an american academy of sleep medicine systematic review, Meta-analysis, and GRADE assessment［J］. J Clin Sleep Med, 2019, 15(2): 301-334.

［5］ McEvoy RD, Antic NA, Heeley E, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea［J］. N Engl J Med, 2016, 375(10): 919-931.

［6］ Guan P, Xu BY, Li YQ, et al. Protective effect of astragalus polysaccharides in model rats of doxorubicin induced cardiac injury［J］. Acta Anatomica Sinica, 2013, 44(5): 685-688. (in Chinese)

关鹏, 徐丙元, 李亚青, 等. 黄芪多糖对阿霉素诱导的心力衰竭模型大鼠的保护作用［J］. 解剖学报, 2013, 44(5): 685-688.

［7］ Guan P, Lin XM, Yang SC, et al. Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation［J］. J Cell Biochem, 2019, 120(3): 3998-4008.

［8］ Liu T, Yang F, Liu J, et al. Astragaloside Ⅳ reduces cardiomyocyte apoptosis in a murine model of coxsackievirus B3-induced viral myocarditis［J］. Exp Anim, 2019, 68(4): 549-558.

［9］ Lin J, Pan X, Huang C, et al. Dual regulation of microglia and neurons by astragaloside Ⅳ-mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury［J］. J Cell Mol Med, 2020, 24(1): 671-685.

［10］ Goes CM, Falcochio P，Drager LF. Strategies to manage obstructive sleep apnea to decrease the burden of atrial fibrillation［J］. Expert Rev Cardiovasc Ther, 2018, 16(10): 707-713.

［11］ Lee SD, Kuo WW, Wu CH, et al. Effects of short- and long-term hypobaric hypoxia on Bcl-2 family in rat heart［J］. Int J Cardiol, 2006, 108(3): 376-384.

［12］ Hang T, Huang Z, Jiang S, et al. Apoptosis in pressure overload-induced cardiac hypertrophy is mediated, in part, by adenine nucleotide translocator-1［J］. Ann Clin Lab Sci, 2006, 36(1): 88-95.

［13］ Pialoux Ⅴ, Hanly PJ, Foster GE, et al. Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans［J］. Am J Respir Crit Care Med, 2009, 180(10): 1002-1009.

［14］ Wang HJ, Tan YZh. Mechanism of autophagy opens a new way for treatment of diseases［J］. Acta Anatomica Sinica, 2017, 48(1): 103-105. (in Chinese)

王海杰，谭玉珍. 细胞自噬机制开启疾病治疗新途径［J］. 解剖学报, 2017, 48(1): 103-105.

［15］ Li B, Chi RF, Qin FZ, et al. Distinct changes of myocyte autophagy during myocardial hypertrophy and heart failure: association with oxidative stress［J］. Exp Physiol, 2016, 101(8): 1050-1063.

［16］ Hariharan N, Ikeda Y, Hong C, et al. Autophagy plays an essential role in mediating regression of hypertrophy during unloading of the heart［J］. PLoS One, 2013, 8(1): e51632.

［17］ McMullen JR, Sherwood MC, Tarnavski O, et al. Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload［J］. Circulation, 2004, 109(24): 3050-3055.

［18］ Li L, Xu J, He L, et al. The role of autophagy in cardiac hypertrophy［J］. Acta Biochim Biophys Sin (Shanghai), 2016, 48(6): 491-500.

［19］ Rabanal-Ruiz Y, Otten EG，Korolchuk Ⅵ. mTORC1 as the main gateway to autophagy［J］. Essays Biochem, 2017, 61(6): 565-584.

［20］ Hahn A, Lauriol J, Thul J, et al. Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: palliative treatment with a rapamycin analog［J］. Am J Med Genet A, 2015, 167A(4): 744-751.