title: Protective effect of hyperoside on cardiac ischemia reperfusion injury through inhibition of ER stress and activation of Nrf2 signaling.
abstract: OBJECTIVE
  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: Tongji University School of Medicine, Shanghai 200092, China.
authors: Jia-Yin
authors: JY
authors: Hou
authors: Tongji University School of Medicine, Shanghai 200092, China; Department of Cardiovascular Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 201318, China.
authors: Ying
authors: Y
authors: Liu
authors: Department of Cardiovascular Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai 201318, China.
authors: Liang
authors: L
authors: Liu
authors: 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.
authors: Xin-Ming
authors: XM
authors: Li
keywords: Cardioprotection; ER stress; Hyperoside; Ischemia/reperfusion injury; Nrf2