Resveratrol attenuates cardiac function impairment in plateau hypobaric hypoxia rats

doi:10.12047/j.cjap.6384.2022.117

Abstract

Abstract: Objective: To study the protective effects of resveratrol (RSV) on cardiac function in rats with high altitude hypobaric hypoxia and its mechanisms. Methods: Thirty-six rats were randomly divided into control group, hypobaric hypoxia group (HH) and hypobaric hypoxia + RSV group (HH+RSV) according to the random number, 12 rats in each group. Rats in the HH and HH+RSV groups were subjected to chronic long-term high altitude hypobaric hypoxia intervention for 8 weeks in a hypobaric chamber at a simulated altitude of 6 000 m for 20 h / d. The rats of HH + RSV were fed with RSV at a dose of 400 mg/(kg·d). The rats were tested once a week for body weight and twice a week for food intake. Before execution, the rats were tested by blood cell analyzer for routine blood parameters and echocardiogram for cardiac function parameters in each group. The routine blood indexes of each group were measured by blood cell analyzer, the cardiac function indexes of each group were measured by echocardiography, myocardial hypertrophy was evaluated by HE staining, myocardial tissue reactive oxygen levels were evaluated by dihydroethidium (DHE) staining. Oxidative stress was evaluated by serum and myocardial tissue total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD) and malondialdehyde (MDA) content. Results: Compared with the C group, the body mass and food intake of rats were decreased significantly (P＜0.05) in HH group, while compared with the C group, RSV had no significant effects on the body mass and food intake of rats in the HH+RSV group (P＞0.05). Compared with the C group, the levels of erythrocytes and hemoglobin of rats in the HH group were increased significantly (P＜0.05), while the platelet concentration was decreased significantly(P＜0.05); compared with the HH group, the erythrocyte and hemoglobin levels were decreased significantly (P＜0.05) and platelet concentration was increased significantly(P＜0.05) in rats of the HH+RSV group. Compared with the C group, the cardiac coefficient, myocardial fiber diameter and thickness were significantly increased in the HH group (P＜0.05); compared with the HH group, the cardiac coefficient and myocardial fiber thickness were significantly decreased in the HH+RSV group (P＜0.05). Echocardiographic analysis showed a significant increase in ventricular wall thickness (P＜0.05) and a significant decrease in ejection fraction and cardiac output (P＜0.05) in the HH group compared with the C group, and a significant decrease in ventricular wall thickness and a significant improvement in cardiac function (P＜0.05) in the HH+RSV group compared with the HH group. The results of DHE staining showed that myocardial tissue reactive oxygen levels were increased significantly in the HH group compared with the C group (P＜0.05); myocardial tissue reactive oxygen levels were significantly restored in the HH+RSV group compared with the HH group (P＜0.05). The oxidative/antioxidant results showed that the serum and myocardial T-AOC and SOD activities were decreased significantly (P＜0.05) and the MDA level was increased significantly (P＜0.05) in the HH group compared with the C group; the serum and myocardial T-AOC and SOD activities were increased significantly (P＜0.05) and the MDA level was decreased significantly(P＜0.05) in the HH+RSV group compared with the HH group. Conclusion: Long-term plateau hypobaric hypoxia exposure leads to myocardial hypertrophy and reduced cardiac function in rats. Resveratrol intervention significantly improves myocardial hypertrophy and cardiac function in rats caused by altitude hypobaric hypoxia exposure, which is closely related to reducing of reactive oxygen species and improving myocardial oxidative stress levels.

Key words: hypobaric hypoxia, Resveratrol, myocardial hypertrophy, echocardiography, rats

CLC Number:

R361.2

XU Hong-bao, SONG Xiao-na, YAN Chang-qing, WANG Guang-rui, PU Ling-ling, WANG Zi-rou, WANG Xin-xing, CHEN Zhao-li, LIU Wei-li. Resveratrol attenuates cardiac function impairment in plateau hypobaric hypoxia rats[J]. CJAP, 2022, 38(6): 644-649.

References

[1] Bilo G, Caravita S, Torlasco C, et al. Blood pressure at high altitude: physiology and clinical implications[J]. Kardiol Pol, 2019, 77(6): 596-603.
[2] Lorell B, Apstein C, Weinberg E, et al. Diastolic function in left ventricular hypertrophy: clinical and experimental relationships[J]. Eur Heart J, 1990, 11(Suppl G): 54-64.
[3] Tasatargil A, Tanriover G, Barutcigil A, et al. Protective effect of resveratrol on methylglyoxal-induced endothelial dysfunction in aged rats[J]. Aging Clin Exp Res, 2019, 31(3): 331-338.
[4] Xu D, Li Y, Zhang B, et al. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats[J]. Int J Med Sci, 2016, 13(12): 942-954.
[5] Chung J, Manganiello V, Dyck J. Resveratrol as a calorie restriction mimetic: therapeutic implications[J]. Trends Cell Biol, 2012, 22(10): 546-554.
[6] Yan C, Wang Z, Liu W et al. Resveratrol ameliorates high altitude hypoxia-induced osteoporosis by suppressing the ROS/HIF signaling pathway[J]. Mol, 2022, 27(17): 538-546.
[7] Genovese A, Alfieri W, Latte S, et al. Regression of myocardial hypertrophy in the rat following removal of acute or chronic hypobaric hypoxia[J]. Eur Heart J, 1982, 3(Suppl A): 161-164.
[8] Flores K, Siques P, Brito J, et al. Lower body weight in rats under hypobaric hypoxia exposure would lead to reduced right ventricular hypertrophy and increased AMPK activation[J]. Front Physiol, 2020, 11: 342-360.
[9] LI Y, Zhou Y, Zhang D, et al. Hypobaric hypoxia regulates iron metabolism in rats[J]. J Cell biochem, 2019, 120(8): 14076-14087.
[10] Siques P, Brito J, Flores K, et al. Long-term chronic intermittent hypobaric hypoxia induces glucose transporter (GLUT4) translocation through AMP-activated protein kinase (AMPK) in the soleus muscle in lean rats[J]. Front Physiol, 2018, 9: 799-813.
[11] Deng B, Liu W, Pu L, et al. Quantitative proteomics reveals the effects of resveratrol on high-altitude polycythemia treatment[J]. Prote, 2020, 20(14): 1335-1346.
[12] Ooi J, Bernardo B, Mcmullen J. The therapeutic potential of miRNAs regulated in settings of physiological cardiac hypertrophy[J]. Future Med Chem, 2014, 6(2): 205-222.
[13] Dolinsky V, Soltys C, Rogan K, et al. Resveratrol prevents pathological but not physiological cardiac hypertrophy[J]. J Mol Med (Berl), 2015 , 93(4): 413-425.
[14] Xie S, Deng Y, Pan Y, et al. Melatonin protects against chronic intermittent hypoxia-induced cardiac hypertrophy by modulating autophagy through the 5' adenosine monophosphate-activated protein kinase pathway[J]. Biochem Biophys Res Commun, 2015, 464(4): 975-981.
[15] Truong V, Jun M, Jeong W. Role of resveratrol in regulation of cellular defense systems against oxidative stress[J]. Bio Factors, 2018, 44(1): 36-49.
[16] Zhang X, Zhang X, Xv J, et al. Crocin attenuates acute hypobaric hypoxia-induced cognitive deficits of rats[J]. Eur J Pharmacol, 2018, 818: 300-305.
[17] Han Y, Jo H, Cho J, et al. Resveratrol as a tumor-suppressive nutraceutical modulating tumor microenvironment and malignant behaviors of cancer[J]. Int J Mol Sci, 2019, 20(4): 925-942.
[18] Wang H, Feng H, Zhang Y. Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis[J]. Neoplasma, 2016, 63(4): 532-539.