Recombinant human erythropoietin combined with bone marrow mesenchymal stem cell transplantation for myocardial damage in sepsis rats

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Abstract

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 cell group, erythropoietin group and erythropoietin + bone marrow mesenchymal stem cell group 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 collected. 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 swelling or shrinkage, and vacuolar degeneration were observed in the model group. Moreover, myocardial interstitial vascular congestion, edema, and inflammatory cell infiltration were visible. Myocardial tissue was similar between erythropoietin and bone marrow mesenchymal stem cell groups, with the presence of mild inflammatory cell infiltration and scattered normal cardiomyocytes. In the erythropoietin + bone marrow mesenchymal stem cell group, 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 cell group 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.

Subject headings:

erythropoietin; mesenchymal stem cells; sepsis; myocytes, cardiac; inflammation

Subject headings:

Teng JL, Li D, Yu HC, Cai SL, Pan XT. Recombinant human erythropoietin combined with bone marrow mesenchymal stem cell transplantation for myocardial damage in sepsis rats. Zhongguo Zuzhi Gongcheng Yanjiu. 2014;18(28): 4530-4534.

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