title: [Effects of N-acetylcysteine on apoptosis induced by myocardial ischemia reperfusion injury in rats' heart transplantation].
abstract: OBJECTIVE
  To investigate the effect of N-acetylcysteine (NAC) on the apoptosis during myocardial ischemia reperfusion injury in rats' heart transplantation, and to explore the possible role of NAC in myocardial apoptosis.
  
  
  METHODS
  Sixty healthy male Lewis rats (weighing, 200-220 g) were randomly divided into 3 groups, 20 rats each group (10 donors and 10 recipients). In control group, 1 mL normal saline was infused via inferior vena cava at 30 minutes before donor harvesting; in donor preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before donor harvesting, but no treatment in recipients; and in recipient preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before recipient transplantation, but no treatment in donors. Heart transplantation was established in each group. Blood was drawn at 6 and 24 hours after reperfusion for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) as markers of graft injury; myocardial tissue was harvested to determine the superoxide dismutase (SOD) and lipid hydroperoxide (LPO) activity at 24 hours after reperfusion and to observe the histology and ultrastructural changes. Graft active Caspase-3 protein expression was measured by immunohistochemistry staining, and apoptosis index (AI) was calculated by TUNEL.
  
  
  RESULTS
  The heart transplantation operation was successfully completed in all groups, and the rats survived to the end of the experiment. The serum levels of AST, ALT, and LDH in donor and recipient preconditioning groups were significantly lower than those in control group at 6 hours after reperfusion (P < 0.05); the levels of AST and ALT in donor preconditioning group and the levels of AST and LDH in recipient preconditioning group were significantly lower than those in control group at 24 hours (P < 0.05); and no significant difference was found between donor and recipient perconditioning groups (P > 0.05). The levels of AST, ALT, and LDH at 24 hours were significantly lower than those at 6 hours in each group (P < 0.05) except the level of ALT in recipient preconditioning group (P > 0.05). SOD activity and SOD/LPO in donor and recipient preconditioning groups were significantly higher than those in control group (P < 0.05), but no significant difference between donor and recipient preconditioning groups (P > 0.05); there was no significant difference in LPO activity among 3 groups (P > 0.05). Histological staining and transmission electron microscope showed that myocardial injury in recipient preconditioning group was obviously lighter than that in donor preconditioning group and control group. Active Caspase-3 in recipient pretreatment group was significantly higher than that in donor preconditioning group and control group (P < 0.05). AI of donor and recipient preconditioning groups was significantly lower than that of control group (P < 0.05), but no significant difference was found between donor and recipient preconditioning groups (P > 0.05).
  
  
  CONCLUSIONS
  NAC can relieve ischemia reperfusion injury in rats' heart transplantation by improving myocardial SOD content, and reducing active Caspase-3 activity and AI, which has a protective effect on myocardial cell of donor heart.
authors.affiliation: Department of Pathology, Basic Medicine School of Hebei United University, Tangshan Hebei 063000, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Hebei United University, PR China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Hebei United University, PR China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Hebei United University, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Hebei United University, PR China.
authors.forename: Gengye
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Hebei United University, PR China.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology, Basic Medicine School of Hebei United University, Tangshan Hebei 063000, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathology, Basic Medicine School of Hebei United University, Tangshan Hebei 063000, PR China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Hebei United University, PR China.
authors.forename: Zhanqing
authors.initials: Z
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D020011:Protective Agents; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D000111:Acetylcysteine