Bone marrow mesenchymal stem cell transplantation effect on expression of HCN2 and HCN4 gene following myocardial infarction / 中国组织工程研究

ABSTRACT

BACKGROUND: Studies have demonstrated that hyperpolarization-activated andcyclic nucleotide-gated cation channels (HCN) 2 and HCN4 are abnormal expressed in ventricular muscle following heart disease, which is closely correlate to ventricular arrhythmia. Bone marrow stem cells (BMSCs) transplantation can improve damaged cardiac muscle; however, its effect on remodeling of ion channel is unclearly. OBJECTIVE: To detect the changes of HCN2 and HCN4 expression in left ventricle following BMSCs transplantation.METHODS: Five Sprague-Dawley (SD) rats, aged 3 weeks, were prepared for BMSCs by Percoll method. Additional 30 health, male, SD rats, were randomly divided into DMEM, cell transplantation, sham operation and control groups. At 4 weeks after model preparation, DMEM culture medium was injected into the infarcted area and surroundings with 5 points in the DMEM group. The 3rd generation of cultured BMSCs (200 μL, with 5×10~6 cells) were injected into rats in the cell transplantation group with the same methods. The mRNA and protein expression of HCN2 and HCN4 gene was detected by RT-PCR and Western blot respectively.RESULTS AND CONCLUSION: In non-infarcted region, the mRNA and protein expression of HCN2 and HCN4 among each groups had no significant difference (P > 0.05). Compared with the control and sham operation groups, mRNA and protein expression of HCN2 and HCN4 in surrounding of the infracted region was elevated in the DMEM group (P < 0.05), which was greater than that of the cell transplantation group (P < 0.05). The mRNA and protein expression of HCN2 and HCN4 was smaller in the center area of infracted region in the DMEM group than that of the control and sham operation groups (P < 0.05), which was similar to the cell transplantation group (P > 0.05). Acute myocardial infarction can increase mRNA and protein expression of HCN2 and HCN4 in infracted region surrounding. BMSCs transplantation may lower the fatality rate of ventricular arrhythmia by reducing HCN2 and HCN4 expression.