Tetramethylpyrazine Combined With Bone Marrow Mesenchymal Stem Cells Transplantation On Angiogenesis And Underlying Mechanisms In Rats With Cerebral Ischemia

Objective To observe tetramethylpyrazine(TMP)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on angiogenesis and neural function in rats with cerebral ischemia and invstigate its possible mechanism.Methods①Isolated and cultured BMSCs by the whole bone marrow adherent method,rats were subjected to middle cerebral artery occlusion(MCAO)for 90 minutes,sham group,model group,BMSCs group,TMP group(40 mg/kg),combined group(40 mg/kg TMP+BMSCs group),n=12.2 h after ischemia,TMP group and combined group were injected with tetramethylpyrazine via the intraperitoneal;24 h after ischemia,sham group and model group were injected with 1 mL PBS,other groups were injected with BMSCs solution of 1mL(1×106 cells)via the tail vein.② Modified neurological severity score(mNSS),adhensive removal test and the corner test were used to evaluate sensorimotor on 1,7,14 and 28 days after ischemia.③ The volume of cerebral infarction were stained with toluidine blue on 28 days after ischemia,the expression of vWF,VEGF and BDNF was detected by immunofluorescence on 14 days after ischemia.④ Real-time fluorescent quantitative PCR and Western Blot detection the expression of VEGF and BDNF mRNA and protein.Results ① The combined group significantly ameliorated neurological dysfunction,the time of adhensive removal and the number of right turn were significantly reduced at 7,14 and 28 days after ischemia(P<0.01 or P<0.05).②Compared with model group and BMSCs group,the infarct volume of combined group was significantly reduced at 28 days after ischemia(P<0.01 or P<0.05).③Compared with model group and BMSCs group,combined group the number of vWF,VEGF and BDNF was significantly increased(P<0.01).④Compared with model group and BMSCs group,the joint group VEGF and BDNF mRNA and protein expression significantly increased(P<0.01).Conclusion ① BMSCs and TMP can improve the neurological function in a rat model of cerebral ischemia;the jointed application can produce a synergistic effect,which is beneficial to the repair of ischemic brain injury.② Combined application can promote angiogenesis in the surrounding area of cerebral infarction.③Mechanisms may be related to the higher expression of VEGF and BDNF mRNA and protein in the surrounding area of cerebral infarction.