Changes of mitochondrial fission and fusion after myocardial injury in cardiac arrest rats / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the dynamic changes of mitochondrial fission and fusion in the heart of cardiac arrest (CA) rats after return of spontaneous circulation (ROSC), and to explore the role of mitochondrial fission and fusion in the myocardial injury after ROSC.Methods:Healthy male SD rats were randomly random number assigned into the post-resuscitation (PR) 4 h ( n=12), PR 24 h ( n=12), PR 72 h ( n=12), and sham groups ( n=6). The rat CA model was induced by asphyxia, and cardiopulmonary resuscitation (CPR) was performed 6 min after CA. The protein expressions of mitochondrial Drp1, Fis1, Mfn1, and Opa1 were determined by Western blot in each group at 4, 24 and 72 h after ROSC. The mRNA expressions of Drp1, Fis1, Mfn1, and Opa1 were determined by RT-PCR. Myocardial ATP content and mitochondrial respiratory function were measured. The histopathologic changes of myocardial tissue were observed under light microscope. One-way analysis of variance (ANOVA) was use to compare quantitative data, and LSD- t test was used for comparison between groups. Results:Compared with the sham group, the protein and mRNA expressions of Drp1 and Fis1 were increased (all P<0.05) and the protein and mRNA expressions of Mfn1 and Opa1 were decreased (all P<0.05) in the PR 4 h and PR 24 h groups. However, there were no statistical differences in the protein and mRNA expressions of Drp1, Fis1, Mfn1, and Opa1 in the PR 72 h group compared with the sham group (all P>0.05). Compared with the sham group, the levels of ATP content [(4.53±0.76) nmol/g protein vs. (8.57±0.44) nmol/g protein and (5.58±0.58) nmol/g protein vs. (8.57±0.44) nmol/g protein] and mitochondrial respiratory control rate [(2.47±0.38) vs. (3.45±0.32) and (2.97±0.24) vs. (3.45±0.32)] were obviously decreased in the PR 4 h and PR 24 h groups (all P<0.05). There were no statistically significant differences in the ATP content [(7.73±0.95) nmol/g protein vs. (8.57±0.44) nmol/g protein] and mitochondrial respiratory control ratio [(3.39±0.34) vs. (3.45±0.32)] between the PR 72 h group and the sham group (all P>0.05). The pathological damage of myocardial tissue was obvious in the PR 4 h group, and was improved significantly in the PR 72 h group. Conclusions:The imbalance of mitochondrial fission and fusion is probably involved in the pathological process of myocardial injury after ROSC, which may be related to mitochondrial dysfunction.