title: [Ischemic postconditioning protects hypertrophic myocardium by ERK1/2 signaling pathway: experiment with mice].
abstract: OBJECTIVE
  To investigate the effects of ischemic postconditioning (IPost) in protecting hypertrophic myocardium subjected to ischemic-reperfusion (I/R) and to study the role of extracellular regulated protein kinase (ERK1/2) in mediating such protection.
  
  
  METHODS
  Transverse aortic constriction (TAC) operation was performed on 12-week-old C57/BL mice to establish left ventricular hypertrophy models. Sixty-four isolated TAC mouse hearts were mounted onto the Langendorff perfusion system and randomly divided into 4 equal group: (1) I/R group undergoing stable perfusion for 30 min, ischemia for 30 min, and re-perfusion for 120 min (an I/R cycle) to cause hypertrophic myocardium I/R injury, (2) IPost group undergoing ischemia for 10s and reperfusion for 10s, totally 3 cycles (60s) before reperfusion for 120 min, (3) I/R+ PD98059 (an ERK1/2 inhibitor) group undergoing perfusion of Krebs-Henseleit (KH) buffer with PD98059 10(-5)mol/L for 15 min and perfusion of KH buffer without PD98059 at the beginning of re-perfusion, and (4) IPost + PD98059 group undergoing 3 cycles of IPost and perfusion of KH buffer with PD98059 10(-5)mol/L for 15 min at the beginning of re-perfusion. Hemodynamic examination was conducted 120 min after re-perfusion to measure the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal uprising velocity of left ventricle pressure (dp/dt(max)), and minimal uprising velocity of left ventricle pressure (dp/dt(min)). After the I/R procedure the myocardium of the left ventricle was isolated to detect the infarction size (IS). Western blotting was used to detect the protein expression of extracellular signal-regulated kinase (ERK) 1/2, phosphorylated ERK1/2, Bcl-2, Bax, and mitochondrial and cytosolic cytochrome (Cyt). C. TUNEL was used to detect the apoptotic rate.
  
  
  RESULTS
  The LVSP and dp/dt(max) levels of the IPost group were (85 +/- 4) mm Hg and (3811 +/- 230) mm Hg/s, both significantly higher than those of the I/R group [(68 +/- 5) mm Hg and (2830 +/- 230) mm Hg/s respectively, both P < 0.05]. Compared with the I/R group, the protein levels of phosphorylated ERK1/2, Bcl-2, mitochondrial CytC of the IPost group were all significantly higher, the protein levels of Bax and cytosolic CytC, and apoptosis index were significantly lower (all P < 0.05), and the IS was smaller (P < 0.05). I/R + PD98059 showed no effects on the above-mentioned parameters. However, the results of the IPost + PD98059 group showed that in the first 15 min of reperfusion addition of PD98059 reversed all changes observed in the IPost group and eliminated the IPost protection by increasing IS to a level similar to that in the I/R group.
  
  
  CONCLUSIONS
  IPost has protective effect in hypertrophic myocardium with I/R injury in vitro. ERK1/2 signaling pathway is involved in the protection of IPost by regulating the myocyte apoptosis.
authors: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
authors: Xiao-Mei
authors: XM
authors: Li
authors: Yi-Tong
authors: YT
authors: Ma
authors: Yi-Ning
authors: YN
authors: Yang
authors: Jian-Fa
authors: JF
authors: Zhang
authors: Bang-Dang
authors: BD
authors: Chen
authors: Fen
authors: F
authors: Liu
authors: Ying
authors: Y
authors: Huang
authors: Wei
authors: W
authors: Han
authors: Xiao-Ming
authors: XM
authors: Gao
mesh_terms: D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3