Modulating effects of preconditioning exercise in the expression of ET-1 and BNP via HIF-1α in ischemically injured brain.

It is well-known that in ischemia-induced hypoxia, hypoxia-inducible factor -1α (HIF-1α) is critical in triggering expression of its downstream target genes to produce several products, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), nitric oxide synthesis (NOS), glucose transportor-1 (GLUT-1), insulin-like growth factor (IGF), which further promote erythropoiesis, angiogenesis, vasodilation and capitalization of glucose to overcome hypoxia. Meanwhile, as the factors with opposite effects on blood vessels, endothelin-1 (ET-1) and brain natriuretic peptide (BNP) also stand out strikingly in ischemic pathophysiology. To this day, several preconditioning manners have been used to induce tolerance to ischemia. During our research, exercise preconditioning was applied and it was demonstrated that HIF-1α triggered expression of ET-1 and BNP, which confirmed their downstream target genes for HIF-1α. And ET-1 may influcence expression of BNP to some degree but not the only factor which regulates BNP expression. Therefore, our findings suggest exercise preconditioning may provide protection to the ischemic brain tissue via HIF-1α which in turn increases expression of BNP to cause vasodilation in cooperation with some other factors, such as VEGF and EPO, to increase the blood flow in the ischemic area and then relieve the injuries induced by ischemia.

Effect of subarachnoid transplantation of bone marrow origin stem cell united with TCM on the gilial cell-line derived neurotrophic factor in brain of cerebal ischemai rats / 国际中医中药杂志

Objective Observe the influence on the Gilial cell-line derived neurotrophic factor (GDNF) after treatment stroke rats with Bone marrow mesenchymal stem cells (BMSCs) or Bone marrow mononuclear cells (BMNCs)combined with traditional Chinese medicine (TCM).Methods Separating and cultivating BMSCs and BMNCs were.140 Wistar rats were divided into 7 groups randomly,normal group,pretended surgery group,model group,BMNC group,BMNC+TCM group,BMSC group,BMSC+TCM group.The other five groups were performed for 2 hours middle cerebral arterial occlusion (MCAO) except normal group and pretended surgery group.Intervention methods in each group after 24 hours of MCAO:model group:Subarachnoid injection of 100 μl 0.01M PBS,BMNC group and BMNC + TCM group,Subarachnoid injection of 2 × 107 BMNCS,BMSC group and BMSC+TCM group,Subarachnoid injection of 2 × 107 BMSCS,BMNC +TCM group and BMSC+TCM group were treated united with TCM on the transplantation day (po.Qd.).GDNF level in all groups' rat brain were analyzed by Enzyme-linked immuno sorbent assay (ELISA) method at the 4th day and the 28th day after transplantation.Results The GDNF level of model group [(62.60±4.05) pg/ml] is higher than normal group's [(53.46 ± 3.91)pg/ml] at the 28th day (P＜ 0.05).The GDNF levels of BMNC group [(194.21 ±39.56)pg/ml,(67.70±4.73)pg/ml] and BMSC group [(169.83±28.84)pg/ml,(82.66±32.23)pg/ml] are higher than model group's at the 4th and 28th day(P＜0.05).The GDNF level of BMSC group is higher than BMNC group's at the 28th day(P＜0.05).The GDNF levels of group BMNC+TCM group[(560.61 ± 194.84) pg/ml,(265.83 ±93.58) pg/ml and BMSC+TCM group[(370.93 ±46.19) pg/ml,(247.34±98.02)pg/ml] are higher significantly than BMNC group's or BMSC group's at the 4th and 28th day(P＜0.05).At the 4th day the GDNF level of the BMNC+TCM group is higher than BMSC+TCM group's(P＜0.05).Conclusion Subarachnoid transplantation of BMNCs or BMSCs will increase the GDNF level in brain of MCAO rats.The transplantantion combined with TCM can inprove the capability of the enhance.That reflect the advantage of transplantantion bone marrow origin stem cell united with TCM.