Rosuvastatin Down Regulates Mitofusin 2 Gene Expression To Inhibit Cardiomyocyte Apoptosis

Background:After acute myocardial infarction(AMI),the inflammatory response is mediated by necrotic myocardium can promote the healing of necrotic myocardium,at the same time, it can also accelerate the remodeling of the myocardium and lead to the apoptosis of myocardial cells through the cascade effect of cytokines, therefore,myocardial apoptosis may be the main form of apoptosis of myocardial cells after infarction. A transmembrane protein of mitochondrial fusion protein 2 on the mitochondrial outer membrane,it is possible to induce apoptosis by activating the mitochondrial apoptotic pathway, inhibiting the Ras-(3-kinase phosphatidylinositol,PI3K)- protein kinase B(PKB/Akt) pathway. In addition to inhibiting the synthesis of alpha hydroxy acid,statins can also inhibit the formation of the isoprenoid,and affect Ras-PI3K/Akt to regulate cell apoptosis, improve vascular endothelial function, anti platelet, anti atherosclerosis etc.Objective:To investigate the influences of Rosuvastatin on myocardial apoptosis index,the expression of mitofusin2(Mfn2) and phosphorylated AKT after acute myocardialinfartion( MI) in rats.Methods:10 SD rats were randomly selected from 60 SD rats and form a sham-operated group. Left anterior descending coronary artery was separated in the sham operation group but with no ligation. The left anterior descending coronary artery of the rest 50 SD rats were ligated and form acute myocardial infarction model. 24 hours later, the survival 41 rats were randomly divided into 3 groups. There were 13 rats in the model group, 14 rats in Statin 1 and 14 rats in Statin 2. After the first day of operation, the Statin 1 and Statin 2 were treated with 1.5mg/(kg.d) and 3.0mg/(kg.d)of Rosuvastatin respectively. The sham operation group and the model group were treated with the same amount of normal saline. After 4 weeks, compare the myocardial apoptosis index, the expression of Mitofusin-2 gene and the expression of phosphorylated AKT of each group. The method of TUNEL was used to detect myocardial apoptosis. The immunohistochemical method was used to detect the expression of Mitofusin-2 gene, and the immunoblotting was designed to detect the expression of phosphorylated AKT.Results:1.Sham group, apoptosis index: 0.00±0.00%; p-Akt gray value: 84.5±5.08; Mfn2 positive index: 4.80 + 0.31%;2.I/R group, apoptosis index: 60.87± 6.13%; p-Akt gray value: 9.52±0.09; Mfn2 positive index: 88.50±1.55%;3.Statin1, apoptosis index: 39.15±3.34%; p-Akt gray value: 17.85±1.18; Mfn2 positive index: 62.48 ±5.58%;4.Statin2, apoptosis index: 26.26±2.97%; p-Akt gray value: 28.35±2.29; Mfn2 positive index: 38.75 ±4.78%.(`x±s)Compared with the sham operation group, myocardial apoptosis condition in sham operation group, AMI group, Statin 1 and Statin 2 group have increased significantly. The expression of p-akt has decreased a lot and the expression of Mitofusin-2 gene has increased significantly(P<0.05). Compared with AMI group,myocardial apoptosis and the expression of Mitofusin-2 gene in Statin 1 and Statin 2group have decreased markedly(P<0.05), but the expression of phosphorylatedAKT has increased. What’s more, compared with Statin 1, Statin 2 varies more significant(P<0.05).Conclusion:Rosuvastatin could suppress myocardial apoptosis of rats after suffering from acute myocardial infarction, and its action strength was dose dependent.