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Danhong injection alleviates hypoxia/reoxygenation induced cardiomyocyte injury by improving mitochondrial dysfunction |
Hits 1125 Download times 809 Received:June 08, 2020 |
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DOI
10.11656/j.issn.1673-9043.2020.05.21 |
Key Words
Danhong injection;mitochondrial energy metabolism;mitochondrial membrane potential;hypoxia/reoxygenation;Akt;ERK1/2 |
Author Name | Affiliation | E-mail | CHEN Ye | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | DUAN Zhenzhen | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | YANG Dongli | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | LI Lin | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, China | einnie_li27@sina.com | LI Yuhong | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, China | yhltcm@126.com |
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Abstract
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[Objective] To study the regulation mechanism of Danhong injection (DHI) on mitochondrial function of cardiomyocytes damaged by hypoxia/reoxygenation (H/R).[Methods] Establishment of H/R injury model of primary myocardial cells. MTT assay was used to detect the effects of DHI on the survival of myocardial cells injured by H/R after intervention with phosphatidylinositol-3-hydroxykinase (PI3K) and MAPK/ERK kinase (MEK) inhibitor LY294002 and PD98059. The effect of DHI on mitochondrial membrane potential (Δφm) in myocardial cells injured by H/R was detected by fluorescent probe Rh123. Western blot was used to detect the effects of DHI on the expression and activation levels of Akt and ERK1/2 proteins,as the downstream proteins of PI3K and MEK,in H/R damaged cardiomyocytes after LY294002 and PD98059 intervention. The effects of DHI on mitochondrial energy metabolism under normal and H/R injury were detected by Seahorse bioenergy detector.[Results] DHI can significantly reverse the cell viability and mitochondrial membrane potential decline caused by H/R. After the intervention of blockers LY294002 and PD98059,the improvement effect of DHI on myocardial cells viability and mitochondrial membrane potential was significantly reduced. DHI significantly increased the phosphorylation levels of Akt and ERK proteins in H/R-damaged cardiomyocytes,and this promotion was inhibited by blockers LY294002 and PD98059. Under normal oxygen condition,DHI did not affect the mitochondrial energy metabolism of cardiac myocytes. However,under H/R conditions,DHI could significantly inhibit the decrease of basal and maximum oxygen consumption rate of cardiomyocytes,and increase the mitochondrial reserve capacity.[Conclusion] DHI could activate Akt and ERK1/2,inhibit mitochondrial energy metabolism disorder,maintain mitochondrial reserve capacity,and alleviate H/R-induced cardiomyocyte damage. |
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