ABSTRACT
BACKGROUND:Bone marrow mesenchymal stem cel s have a low survival rate after implanted into the ischemic myocardium. However, hypoxia preconditioning (HPC) may enhance bone marrow mesenchymal stem cel proliferation and promote its survival rate. OBJECTIVE:To explore whether Pim-1 is involved in HPC protecting against apoptosis of bone marrow mesenchymal stem cel s and the relevant mechanism. METHODS:Bone marrow mesenchymal stem cel s were respectively subjected to HPC for 0, 6, 12, and 24 hours. The expression of Pim-1 and apoptosis-related genes were detected by RT-qPCR and western blot. Then, the best hypoxic preconditioning time was determined as 12 hours. Then, bone marrow mesenchymal stem cel s were assigned to one of the fol owing groups:control (without HPC), 12-hour HPC, 12-hour HPC+Pim-1 inhibitor groups. Flow cytometry analysis was used to detect the cel apoptosis, Transwel assay to analyze the cel migration ability in each group, and JC-1 kit to detect mitochondrial membrane potential. Animal models of myocardial infarction were established. One week after modeling, bone marrow mesenchymal stem cel s were given via multi-point injection around the infarct zone of rats. Two weeks after modeling, heart tissues of rats were taken and sliced fol owed by DiI staining to calculate the survival rate of bone marrow mesenchymal stem cel s. Additional y, rat cardiac function was assessed by echocardiography prior to and after modeling as wel as at 4 weeks after cel transplantation. RESULTS AND CONCLUSION:At 12 hours after HPC, the expression of Pim-1, p-Akt and Bcl-2 gene in the infarct region was significantly increased, but the expression of caspase-3 and Bax was significantly decreased. Compared with the control group, cel viability in the 12-hour HPC group was increased very significantly at 1 week after cel transplantation (P<0.001), the migration and anti-apoptosis ability were enhanced significantly (P<0.01) and the cardiac function of rats was significantly improved in the 12-hour HPC group (P<0.05). Al of these protective effects were blocked by the Pim-1 inhibitor. These findings indicate that HPC can protect bone marrow mesenchymal stem cel s from apoptosis through activating Akt and up-regulating Pim-1, and thereby improve the therapeutic effect of bone marrow mesenchymal stem cel transplantation on ischemic heart diseases.