RESUMO
BACKGROUND:Erythropoietin and bone marrow mesenchymal stem cells have been shown to affect myocardial apoptosis. However, few studies concerned their combined application to sepsis-related myocardial injury. OBJECTIVE:To observe the effects of the combination of erythropoietin and bone marrow mesenchymal stem cells on pathology and apoptosis of sepsis rat cardiomyocytes. METHODS:A total of 50 Sprague-Dawley rats were randomly selected and assigned to five groups (n=10). Sepsis models were established by cecal ligation perforation method. Rat models in the bone marrow mesenchymal stem cellgroup, erythropoietin group and erythropoietin+bone marrow mesenchymal stem cellgroup were respectively treated with bone marrow mesenchymal stem cells, erythropoietin and erythropoietin+bone marrow mesenchymal stem cells immediately after model induction via intraperitoneal injection or caudal vein. Model group received cecum ligation and puncture. Control group did not undergo any treatment after the abdomen was opened. Model and control groups were infused with an equal volume of physiological saline via caudal vein. At 24 hours, experimental animals were sacrificed by anesthesia. Myocardial specimens were col ected. Myocardial appearance was observed using hematoxylin-eosin staining. Bax, Caspase-3 and Bcl-2 were tested by western blot assay. RESULTS AND CONCLUSION:Hematoxylin-eosin staining:cardiomyocytes were regularly arranged, showing integrated structure in the control group. Extensive myocardial fiber breakage, disordered arrangement, cardiomyocyte swel ing or shrinkage, and vacuolar degeneration were observed in the model group. Moreover, myocardial interstitial vascular congestion, edema, and inflammatory cellinfiltration were visible. Myocardial tissue was similar between erythropoietin and bone marrow mesenchymal stem cellgroups, with the presence of mild inflammatory cellinfiltration and scattered normal cardiomyocytes. In the erythropoietin+bone marrow mesenchymal stem cellgroup, cardiomyocytes were slightly damaged. Interstitial vascular congestion was not apparent, and a few inflammatory cells infiltrated. Western blot assay results demonstrated that Bcl-2 protein expression was significantly higher (P<0.01), but Bax and Caspase-3 protein expression was lower (P<0.05) in the erythropoietin+bone marrow mesenchymal stem cellgroup than in the erythropoietin, model and control groups. The combination of erythropoietin and bone marrow mesenchymal stem cells in treatment of sepsis-related myocardial injury could lessen myocardial pathological changes, and inhibit cardiomyocyte apoptosis. The mechanisms maybe exert by upregulating anti-apoptotic protein expression and downregulating apoptotic protein expression.