体外放散式冲击波促进脑梗死大鼠海马区神经干细胞增殖并抑制miR-124的表达

Radial extracorporeal shock wave therapy promotes the proliferation of neural stem cells in hippocampus of cerebral infarction rats and inhibits miR-124 expression

背景:miR-124在神经干细胞的增殖中发挥重要作用,并且脑梗死后在脑组织及血液中的表达发生变化,提示其是脑梗死后内源性神经再生的核心调控因子之一。体外放散式冲击波可以促进神经干细胞增殖,但是否与miR-124有关目前尚不明确。目的:探讨体外放散式冲击波对脑梗死后海马区miR-124表达的影响及其促进神经干细胞的增殖是否与miR-124有关。方法:建立大鼠大脑中动脉栓塞模型,脑梗死大鼠随机分为体外放散式冲击波组与对照组。体外放散式冲击波组在脑梗死后72 h干预缺血侧头部,每3 d干预1次,于造模成功后的11,20,29,38 d进行大鼠神经功能评分;采用RT-qPCR法检测脑梗死大鼠患侧海马miR-124与Nestin mRNA的表达;Western blot和免疫荧光技术检测患侧海马Nestin蛋白的表达。结果与结论:①大鼠脑梗死后,患侧海马miR-124表达逐渐增加;②大脑中动脉栓塞后11,20,29,38 d,体外放散式冲击波组大鼠改良神经功能缺损评分均低于对照组(P<0.05),患侧海马Nestin表达均高于对照组(P<0.05);③大脑中动脉栓塞后11,20,29 d,体外放散式冲击波组脑梗死大鼠患侧海马miR-124表达低于对照组(P<0.05);④结果表明,脑梗死大鼠患侧海马miR-124表达增高,冲击波直接干预脑梗死大鼠患侧头部可降低miR-124表达,促进神经干细胞数目增多,改善受损神经功能。

BACKGROUND:miR-124 plays an important role in the proliferation of neural stem cells and changes in brain tissue and blood expression after cerebral infarction,suggesting that it is one of the core regulators of endogenous nerve regeneration after cerebral infarction.Radial extracorporeal shock wave therapy can promote neural stem cell proliferation,but whether it is related to miR-124 is currently unclear.OBJECTIVE:To investigate the effect of radial extracorporeal shock wave therapy on the expression of miR-124 in the hippocampus after cerebral infarction and whether the promotion of neural stem cell proliferation is related to miR-124.METHODS:A model of middle cerebral artery occlusion in rats was established.Rats were randomly divided into radial extracorporeal shock wave group and control group.The radial extracorporeal shock wave group was subjected to radial extracorporeal shock wave therapy intervention,with the ischemic head 72 hours after the cerebral infarction,once every 3 days.At 11,20,29,and 38 days after model establishment,modified neurological function scores were assessed in rats.Then RT-qPCR was used to detect the expressions of miR-124 and Nestin mRNA in the hippocampus of cerebral infarction rats.Western blot assay and immunofluorescence were used to detect the expression of Nestin protein in the hippocampus of the ischemic side.RESULTS AND CONCLUSION:(1)After cerebral infarction in rats,the expression of miR-124 gradually increased in the hippocampus of the ischemic side.(2)At 11,20,29,and 38 days after middle cerebral artery occlusion,the neurological scores of the rats were lower in the radial extracorporeal shock wave group than those in the control group(P<0.05).The expression of Nestin was higher on the ischemic side of the hippocampus than that in the control group(P<0.05).(3)At 11,20 and 29 days after middle cerebral artery occlusion,the expression of miR-124 in hippocampus of cerebral infarction rats on the affected side in the radial extracorporeal shock wave group was lower than that of the control group(P<0.05).(4)Results suggest that expression of miR-124 in the hippocampus of cerebral infarction rats is increased.Radial extracorporeal shock wave therapy directly interfering with the head of the affected side can reduce the expression of miR-124,increase the number of neural stem cells,and improve impaired nerve function.