Jia-Yin Hou1, Ying Liu2, Liang Liu3, Xin-Ming Li4. 1. Tongji University School of Medicine, Shanghai 200092, China. 2. Tongji University School of Medicine, Shanghai 200092, China; Department of Cardiovascular Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 201318, China. 3. Department of Cardiovascular Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 201318, China. 4. Tongji University School of Medicine, Shanghai 200092, China; Department of Cardiovascular Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 201318, China. Electronic address: zpxinmingli@163.com.
Abstract
OBJECT: To study the protective effect of hyperoside (Hyp) on cardiac ischemia reperfusion injury and its potential mechanism. METHODS: Rats were divided into two groups for the evaluation, the Hyp (50 μM Hyp; n = 8) and the control group (n = 8). Rat hearts were isolated and perfused with Krebs-Henseleit buffer (KHB) for 30 min. After being inhibited with cardioplegic solution, they were stored for 4 h in B21 solution at 4 °C. Afterwards, rat hearts were perfused with KHB again for 45 min. In this period, Hyp was added into solutions of cardioplegia for storage and KHB. Parameters of cardiac functions, including heart rate, the systolic pressure of the left ventricle, the end-diastolic pressure of the left ventricle, the developed pressure of the left ventricle, the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded. The levels of adenosine triphosphate (ATP), the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury. Moreover, cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion. What were analyzed included the endoplasmic reticulum (ER) stress hallmarks expressions, such as binding immunoglobulin protein and C/EBP homologous protein, using the western blot and real-time PCR. Besides, the NF-E2-related factor 2 (Nrf2) expression was measured to explore the potential mechanism. RESULTS: Compared with the control group, the Hyp group had better cardiac functional parameters and higher ATP levels; pretreatment of Hyp greatly relieved the apoptosis of myocyte, decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent. CONCLUSIONS: Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue, easing oxidative injury of myocardium and reducing apoptosis following IRI dramatically, while the ER stress inhibition and the downstream Nrf2 signaling activation may contribute to the effects of protection.
OBJECT: To study the protective effect of hyperoside (Hyp) on cardiac ischemia reperfusion injury and its potential mechanism. METHODS:Rats were divided into two groups for the evaluation, the Hyp (50 μM Hyp; n = 8) and the control group (n = 8). Rat hearts were isolated and perfused with Krebs-Henseleit buffer (KHB) for 30 min. After being inhibited with cardioplegic solution, they were stored for 4 h in B21 solution at 4 °C. Afterwards, rat hearts were perfused with KHB again for 45 min. In this period, Hyp was added into solutions of cardioplegia for storage and KHB. Parameters of cardiac functions, including heart rate, the systolic pressure of the left ventricle, the end-diastolic pressure of the left ventricle, the developed pressure of the left ventricle, the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded. The levels of adenosine triphosphate (ATP), the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury. Moreover, cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion. What were analyzed included the endoplasmic reticulum (ER) stress hallmarks expressions, such as binding immunoglobulin protein and C/EBP homologous protein, using the western blot and real-time PCR. Besides, the NF-E2-related factor 2 (Nrf2) expression was measured to explore the potential mechanism. RESULTS: Compared with the control group, the Hyp group had better cardiac functional parameters and higher ATP levels; pretreatment of Hyp greatly relieved the apoptosis of myocyte, decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent. CONCLUSIONS: Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue, easing oxidative injury of myocardium and reducing apoptosis following IRI dramatically, while the ER stress inhibition and the downstream Nrf2 signaling activation may contribute to the effects of protection.
Authors: Man Liu; Guangbin Shi; Anyu Zhou; Cassady E Rupert; Kareen L K Coulombe; Samuel C Dudley Journal: J Mol Cell Cardiol Date: 2018-02-21 Impact factor: 5.000
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