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CJAP ›› 2017, Vol. 33 ›› Issue (1): 40-46.doi: 10.12047/j.cjap.5448.2017.010

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Role of changes in sodium pump activity and endoplasmic reticulum stress in the ischemia/reperfusion induced injury of isolated hearts

WANG Hai-hua1, WANG Hai-zhen1, SHI Na1, WANG Zhu-qing2, WANG Yao-jun2, ZHOU Ping-ping1, WANG Jing1   

  1. 1. Department of Physiology, Wannan Medical College, Wuhu 241002, China;
    2. Department of Clinical Medicine, Wannan Medical College, Wuhu 241002, China
  • Received:2016-02-06 Revised:2016-10-19 Online:2017-01-28 Published:2018-06-19
  • Supported by:
    安徽省高校省级科学研究重点项目(KJ2016A729,KJ2013A251);安徽省级大学生创新创业训练计划项目(AH201310368107);国家级大学生创新创业训练计划项目(201510368009)

Abstract: Objective: To investigate the roles of change in sodium pump activity and endoplasmic reticulum stress (ERS) in ischemia/reperfusion (I/R) injury of the isolated rat hearts.Methods: Sixty male SD rats were randomly divided into 6 groups (n=10 each):normal control group (NC), I/R group (I/R), ouabain-I/R group (OUA-I/R), anti-digoxin antiserum-I/R group (Anti-Dig-I/R), PP2 (Src kinase inhibitor)-ouabain-I/R group (PP2-OUA-I/R),U73122 (PLC inhibitor)-ouabain-I/R group (PP2-OUA-I/R). The isolated rat hearts were perfused on the Langendorff apparatus. Except for NC group, all the hearts were subjected to 30 min global ischemia and followed by 120 min reperfusion. The cardiac function indexes were recorded at the same time. The coronary effluent was collected for estimating the activity of lactate dehydrogenase (LDH) and creatine kinase (CK). The activity of Na+-K+-ATPase and intracellular calcium concentration in myocardial tissue were measured. Apoptosis was evaluated by Flow cytometric analysis. The expressions of sodium pump α1 subunit, glucose regulated protein(GRP78),C/EBP homologous protein (CHOP) and Bcl-2/Bax were determined by Western blot.Results: Pretreatment with ouabain significantly reduced the recovery of cardiac function, increased the levels of CK, LDH and intracellular calcium concentration, decreased the activity of Na+-K+-ATPase. In addition, ouabain markedly increased the myocardial apoptosis index, down-regulated the expressions of sodium pump α1 subunit and Bcl-2, up-regulated the expressions of GRP78,CHOP and Bax; while these changes were significantly improved in the Anti-Dig-I/R group compared with those in the I/R group; PP2 or U73122 partially blocked the effects of ouabain on myocardial I/R injury. Compared with the OUA-IR group, the recovery of cardiac function, the activity of Na+-K+-ATPase and the expressions of sodium pump α1 subunit and Bcl-2 were significant higher, meanwhile the leakage of CK and LDH, intracellular calcium concentration, myocardial apoptosis index and the expressions of GRP78 and Bax were significantly lower in PP2-OUA-I/R and U73122-OUA-I/R group.Conclusion: Changes in sodium pump function and endoplasmic reticulum stress all participate in the process of I/R injury. Current findings further suggest that sodium pump mediates ERS by activating signals of Src and PLC pathway, which may be one of the mechanisms of apoptosis induced by I/R injury.

Key words: sodium pump, endoplasmic reticulum stress, ischemia/reperfusion injury, isolated heart, apoptosis, mouse

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