title: [Amelioration of myocardial ischemia/reperfusion injury by leptin pretreatment and ischemic preconditioning in mouse].
abstract: OBJECTIVE
  To study the effects and role of leptin pretreatment and ischemic preconditioning (IPC) on the reduction of myocardial ischemia/reperfusion injury (MIRI) in mouse.
  
  
  METHODS
  Thirty-six male C57BL/6 mice were randomized into five groups: (1)sham operation group (n=12); (2) brief ischemia/reperfusion (I/R) treatment group (n=6), in which the mice were subjected to three cycles of a 3-minute regional ischemia followed by a 5-minute reperfusion (I/R cycle); (3) MIRI group (n=6), in which MIRI was established in the mice by blocking anterior descending branch of left coronary artery for 30 minutes, followed by 120 minutes reperfusion; (4) IPC group (n=6), in which three I/R cycles were performed on the mice followed by the MIRI protocol; (5) leptin pretreatment group (leptin group, n=6), in which 50 microg/kg of leptin was injected intraperitoneally to the mice 30 minutes before myocardial ischemia. From 6 mice of the sham operation group and from the mice of brief I/R group, serum samples were collected at different time points (0, 5, 30 and 120 minutes) after reperfusion to measure changes in serum leptin level. From the rest of the mice, blood and heart samples were harvested at 120 minutes after reperfusion to analyze the myocardial function and infarct size, leptin, myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels.
  
  
  RESULTS
  IPC procedure resulted in an increase in serum leptin level shortly after reperfusion. The leptin level increased significantly than that of sham operation group [(6.24+/-2.34) microg/L vs. (1.35+/-0.45) microg/L] at 5 minutes after I/R, and reached the peak value of (12.36+/-1.33) microg/L at 30 minutes after I/R. Then it gradually decreased to its original (0 minute after reperfusion) value [(1.96+/-1.33) microg/L] at 120 minutes after I/R. There was no difference compared with sham operation group [(1.16+/-0.25) microg/L, P>0.05]. Administration of leptin or IPC before MIRI significantly reduced infarct size [(11.50+/-2.26)%, (9.00+/-1.90)% vs. (37.00+/-2.53)%], the myocardial leptin levels [(8.36+/-3.42) microg/g, (6.71+/-2.03) microg/g vs. (15.51+/-3.92) microg/g], MPO [(17.10+/-3.95) microg/g, (13.33+/-2.88) microg/g vs. (30.83+/-4.06) microg/g], serum leptin levels [(15.03+/-1.87) microg/L, (11.85+/-0.72) microg/L vs. (29.55+/-2.31) microg/L], serum TNF-alpha [(35.10+/-10.12) ng/L, (27.04+/-5.18) ng/L vs. (81.34+/-14.20) ng/L], and IL-6 levels [(167.39+/-72.83) ng/L, (149.13+/-37.69) ng/L vs. (477.30+/-29.09) ng/L, all P<0.01].
  
  
  CONCLUSIONS
  Pretreatment using leptin results in preconditioning-like tolerance against infarction dysfunction. This cardiac protection effect is mediated, in part, via suppression of inflammation in preconditioned myocardium.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Guilin Medical College, Guilin 541001, Guangxi, China.
authors.forename: Tong-tong
authors.initials: TT
authors.lastname: Xu
authors.forename: Shi-ping
authors.initials: SP
authors.lastname: Liu
authors.forename: Xiao-shan
authors.initials: XS
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D019157:Ischemic Preconditioning, Myocardial; D020738:Leptin / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha