Protection Of Bone Marrow Mesenchymal Stem Cells Transplantation Combined With Bone Marrow Stem Cells Mobilization On Liver Cells In Rats With Severe Acute Pancreatitis

Objective:To observe the protective effects of autologous bone marrow mesenchymal stem cells transplantation combined with bone marrow stem cells mobilization on liver cell in rats with severe acute pancreatitis, and explore their mechanism.Method:240 SD rats with severe acute pancreatitis were prepared by injecting intraperitoneally with L-arginine and randomly divided into sham-operated group (n=48), model control group(n=48), bone marrow mesenchymal stem cell transplanted (MSC) group (n=48), Granulocyte-Colony Stimulating Factor treated (G-CSF) group (n=48) and MSC+G-CSF (n=48). MSC group were prepared via injection of 1.2ml MSC to femoral vein 6 hours after SAP, G-CSF group were prepared via subcutaneous injection of G-CSF 40μg/kg for 3 days before SAP, MSC+G-CSF group combined use of MSC and G-CSF, sham-operated group were injected of equal volume normal saline. According to the difference of time points after operation, the rats in each group were subdivided into 12 h,24 h,48 h and 72 h groups (n=12). At various time points after operation, the mortality rate, pathological changes, expression levels of Bax, Bcl-2 proteins and apoptosis indexes of livers were observed respectively. The contents of serum TNF-a, IL-6, ALT, AST, LDH and CRP were simultaneously determined to compare the difference of each group by variance analysis.Results:Compared to the respective model group, the mortality rates of all treated group at 72h showed no difference(P>0.05), but no rats died before 48h; the pathological injurys of liver cells were relieved than control group; the liver cell apoptosis indexes of MSC+ G-CSF group at 48h and 72h were 107.1±7.0,110.3±8.6, the expression of Bax in livers at 24h,48h and 72h was 5.60±0.25,5.69±0.22,5.73±0.27, Bcl-2 protein at 48h,72h was 4.61±0.28,4.43±0.28, the difference compared to MSC and G-CSF group was significant(P<0.05); the serum TNF-a, IL-6, ALT, AST, LDH and CRP decreased obviously at 24h/48h of each treated group(P<0.05), MSC+G-CSF group showed a more significant action to each indexs than MSC group and G-CSF group after 48 h (P<0.05), but no marked difference were observed between the latter two groups (P>0.05).Conclutions:Autologous bone marrow mesenchymal stem cells transplantation combined with bone marrow stem cells mobilization can significantly protect livers from severe damage in the progress of severe acute pancreatitis, the probable mechanisms are related to pathological regeneration, anti-inflammatory effect and apoptosis inhibition of MSC.