Effect of H₂ O₂ Pretreatment of Autologous Mesenchymal Stem Cells Transplantation on Ventricular Remodeling After Acute Myocardial Infarction

Objective: H ₂ O ₂ pretreatment bone marrow mesenchymal stem cells (mesenchymal stem cells, MSCs), in the acute phase of myocardial infarction after transplantation, and study its acute myocardial infarction ventricular remodeling after impact, and a preliminary study of its mechanism. Methods: In vitro: the third generation of MSCs placed in 24-well plates Petri dish culture, respectively, to 0 μmol / L, 20μmol / L, 50μmol / L, 100μmol / L, 200μmol/LH _{2 the O 2 pretreatment MSCs cultured 72h, MSCs supernatant was measured by ELISA of vascular endothelial growth factor (vascular endothelium growth factor, VEGF), hepatocyte growth factor (hepatocyte growth factor, HGF) the concentration;, were given H the 2 O 2 pretreatment of MSCs 0h, 12h, 24h, 36h, 48h for 72h by ELISA MSCs supernatant VEGF, HGF concentration. In vivo testing: 20 healthy Taihu Meishan pigs, attentive catheter with gelfoam anterior descending coronary artery (left anterior descending coronary artery, LAD) the second diagonal branch establishment of the pig acute myocardial infarction model, were randomly divided into four groups: in the MI District injection DMEM interventional group A (control group): myocardial infarction after 24h; B group (oxidized the stem cell supernatants group): 24 hours after MI injection after the H 2 O 2 pretreatment of MSCs in culture supernatants; C group (stem cell group): 24h transplantation after myocardial infarction untreated MSCs; D group (oxidized stem cell group): 24 hours after myocardial infarction transplant after H < sub> 2} O ₂ preconditioning MSCs. Each group at different time points were measured by ELISA serum levels of tumor necrosis factor-α (tumor necrosis factor alpha, TNF-α) concentration. Myocardial infarction before 24 hours after myocardial infarction, stem cell transplantation 4w line Powerlab Millar, pressure catheter and magnetic resonance detection of cardiac function index. 4w get pig heart stem cell transplantation the TTC measure myocardial infarct size, immunohistochemical staining to detect non-infarct zone of matrix metalloproteinase-9 (matrix metalloproteinase-9, MMP-9) and inhibit the enzyme -1 (tissue inhibitors of matrix metalloproteinases metalloproteinase-1, TIMP-1) expression of vWF (von Willebrand factor, vWF) immunohistochemistry count neovascularization density. Results: In vitro: different concentrations of H ₂ O ₂ pretreatment of MSCs, 20μmol / L group, VEGF, HGF concentration compared with 0 μmol / L,, 50 μmol / L, the 100μmol / L, 200μmol / L group was significantly higher (p lt; 0.05); the H ₂ O ₂ pretreatment of MSCs in different time 24h group VEGF, HGF concentration than 0h, 12h, 36h, 48h group was significantly higher (p lt; 0.05). The concentration of serum TNF-α in vivo test: D and B group the same point in time than the A and group C lower (p lt; 0.05). After transplantation 4w D group and group B compared with group A, left ventricular pressure rise and decline of the maximum rate (dp / dtmax, -dp/dtmax), left ventricular developed pressure (left ventricular developed pressure, LVDP) and end-diastolic wall thickness (end-diastolic wall thickness, EDWT), stroke output (stroke volume, SV) expression was significantly increased (p lt; 0.05), myocardial MMP-9 protein expression and myocardial infarct size is significantly reduced compared with group A (p lt ; 0.05), myocardial expression of TIMP-1 protein expression and infarct peripheral zone capillary density was significantly increased (p lt; 0.05); and D compared with group B, D improved more significantly (p lt; 0.05); C group, these indicators compared with group A, no significant improvement. Conclusion: 1,20 μmol of / LH ₂ O ₂ the pretreatment MSCs24h can enhance cytokine VEGF, HGF secretion. 2, the acute phase after MI transplant H ₂ O ₂ pretreatment of MSCs, reducing the level of expression of the proinflammatory cytokines, reducing ventricular matrix remodeling, improve the blood of the infarct border zone supply, thereby inhibiting ventricular remodeling. 3, the acute phase after MI transplantation H ₂ O ₂ pretreated MSCs significantly improved cardiac function, part of the mechanism may be H ₂ O < sub> 2 pretreatment increased secretion of cytokines MSCs.