Effect Of BMSCs Intravenous Transplantation On DMCAO Rats And Its Early Mechanism

Objective:To explore the curative effect and early mechanism of allogeneic bone marrow mesenchymal stem cells (BMSCs) transplanting intravenouslyin rats which underwent distal middle cerebral artery occlusion (dMCAO).Methods:A total of 90 Sprague Dawley (SD) male rats were divided into sham group (30 cases), control group (30 cases) and marrow mesenchymal stem cells(BMSCs)transplanted group (30 cases)randomly.Cerebral infarction models were made through occluding distal middle cerebral artery(dMCAO).One hour later, the BMSCs was transplanted through the tail vein. The brain slices were TTC stained and the cerebral infarction volumes were calculated at 48 h after dMCAO. At the 1st,3rd,5th and 7th day after the dMCAO, behavioral tests such ascylinder test, grid walking test and beam balance test were performed. The amount of microglia was calculated in the immunohistochemically stained peri-ischemia cortex area at 48h after the dMCAO and the IGF-1 and bFGF concentration wasdetected in the same area using ELISA. At the 2nd,4th, and l^day, the inflammatory cytokines (IL-4、IL-6、IL-10、IL-1βand TNF-a) in brain tissue and peripheral blood were detected using ELISA.Results:The cerebral infarction volumes were significantly smaller in BMSCs group than those in control group (P< 0.05). At the early stage of dMCAO, the behaviorsof BMSCs group was significantly superior to those of control group in cylinder test(the 1st,3rd and 5th day after dMCAO) and grid walking test (the 1st and 3rd day after dMCAO)(P< 0.05),while, the two groups showed no statistical difference at 7th day after dMCAO. Nostatistical difference was detected between the two groups in beam balance test. In the peri-ischemia cortex infarct area, the concentration of nutrition factors such as IGF-1 and bFGF in BMSCs group was significantly higher than that in ischemia group. No statistical difference was shown between the number of microglia in BMSCs group andthat in control group in peri-ischemia cortex infarct area. In peripheral blood, compared with the control group,the levels of some inflammatory factors inthe BMSCs group were detected and the results were as following:(1) Atthe 2nd day, the level of IL-6 was increased significantly(P<0.05). At the same time, the levels of IL-4 were decreasedwhile the TNF-α was increased,but had no statistical significance. (2) At the 4th day, the level of IL-6 was increased significantly (P<0.05). At the same time, the levels ofTNF-α and IL-1β were increased,but had no statistical difference. (3) At the 7th day, the level of IL-10 was increased,but had no statistical significance, while, the lsvels ofTNF-α andIL-1β were reducedobviously (P<0.05). In brain tissue, compared with the control group,the levels of some inflammatory factors inthe BMSCs group were detected and the results were as following:(1) Atthe 2nd day, the level of IL-6 was decreased, but had no statistical significance. (2) At the 4th day, the levels of IL-10, TNF-α and IL-1β were increased,but had no statistical difference. (3) At the 7th day,the levels of IL-4, IL-6 and TNF-α were decreased,however,had no statistical significance. The data was analyzed using SPSS 19.Conclusion:BMSCs transplantationintravenously can reduce the infarction volume and improve the behavior of dMCAO rat. This may be mainly due to the effect of elevated IGF-1、bFGF in the brain of BMSCstransplanted rats. At the 7th day, the levels ofTNF-α andIL-1β were reducedobviously in peripheral bloodmaybe because of the anti-inflammatory effect ofBMSCs.