骨髓间充质干细胞静脉移植治疗大鼠脑梗死的机制研究

目的 观察炎性因子和营养因子在静脉植入同种异体骨髓间充质干细胞(MSC)治疗大鼠脑梗死中的作用.方法 采用大脑中动脉远端阻塞法(dMCAO)制作大鼠脑梗死模型,假手术组开颅但不凝断血管、移植组于造模后1h经尾静脉移植1×106大鼠骨髓MSC,缺血对照组注射等量生理盐水.移植后48 h取脑用ELISA法检测皮层梗死核心区及纹状体促炎因子TNF-α、IL-1β、IFN-γ、IL-6,抗炎因子IL-4、IL-10,以及营养因子IGF-1、GDNF、BDNF的含量.结果 同种异体骨髓MSC移植后48 h,和缺血对照组比较,移植组脑梗死区炎性因子IFN-γ、IL-6显著降低,TNF-α、IL-1β显著升高,纹状体区IL-10显著下降.移植组梗死区BDNF的含量比缺血对照组显著增高,纹状体区IGF-1的含量也比缺血对照组显著升高;GDNF在各组间无显著差异.结论 脑梗死后1h同种异体静脉移植骨髓MSC治疗dMCAO模型,其梗死后48 h时间点的治疗效果和MSC抑制炎性反应没有明确联系,而更可能和大鼠脑内营养性细胞因子增加有关.

Mechanism of therapeutic effects of intravenous transplantation of bone marrow derived mesenchymal stromal cells on ischemia in rats

Objective To study effects of inflammatory cytokines and neurotrophic factors on intravenous transplantation of allogeneic bone marrow derived mesenchymal stromal cells (MSC) treatment of ischemia in rats.Methods The distal middle cerebral artery occlusion (dMCAO) was applied in this study by electrocoagulation.For the transplantation group,1 × 106 allogeneic MSC were intravascular transplanted into tail vein at 1 h after ischemia onset.The ischemia vehicle group received dMCAO surgery and intravascular saline injection.At 48 h after ischemia onset,the levels of pro-inflammatory cytokines (TNF-α,IL-1 β,IFN-γ,IL-6),anti-inflammatory cytokines (IL-4,IL-10),and neurotrophic factors (IGF-1,GDNF,BDNF) were measured in the ischemia cortex area and striatum by ELISA.Results At 48 h after ischemia onset,as compared with core area of ischemia vehicle group,allogeneic MSC decreased the levels of IFN-γ,IL-6 significantly,increased the levels of TNF-α,IL-1β,BDNF significantly.MSC also reduced the levels of IL-10,while increased IGF-1 significantly in striatum.No significant difference of GDNF was found between ischemia vehicle and MSC transplantation group.Conclusions Allogeneic MSC is beneficial to the ischemia damaged brain if transplanted at 1 h after the onset of ischemia.The effects of anti-inflammation are not the underlying mechanisms of the therapeutic effects at this time.That increased of IGF-1 and BDNF after MSC transplantation in the ischemia core of cortex area may contribute to the therapeutic effects of MSC transplantation group.