运动训练诱导miR-210和BDNF的表达对脑缺血缺氧后新生鼠血管再生的机制研究

Mechanism of exercise training-induced miR-210 and BDNF expression on angiogenesis in neonatal rats after cerebral ischemia and hypoxia

目的探讨运动训练对新生鼠在缺氧缺血性脑损伤(HIBD)后微小RNA210(miR-210)、脑源性神经生长因子(BDNF)和血管内皮生长因子(VEGF)表达的影响。方法采用Rice-Vannucci法制备新生鼠HIBD模型,分为对照组(C)、假手术组(S)、模型组(M)和运动训练组(T),造模7 d后开始训练1周、2周,取脑组织后采用HE染色观察脑细胞的病理改变,免疫组化法检测脑组织BDNF和VEGF的表达,实时定量荧光PCR检测脑组织miR-210表达水平。结果C组和S组大脑组织结构清晰,造模后神经细胞出现变性和坏死。T组和M组在各时间点与S组比较,miR-210、BDNF和VEGF的表达差异具有统计学意义(P<0.05)。T组和M组中随着时间的延长,miR-210、BDNF和VEGF的表达呈上升趋势,在14 d和21 d后T组和M组比较,上述指标表达差异均有统计学意义(P<0.05)。VEGF表达与miR-210和BDNF呈明显正相关(r=0.841,0.818,P均<0.01)。结论运动训练干预新生小鼠缺氧缺血脑损伤可增加miR-210和BDNF的表达,进而促进脑组织VEGF表达,最终对神经损伤起到保护作用。

Objective To investigate the influence of exercise training on the expression of microRNA210(miR-210),brain-derived nerve growth factor(BDNF)and vascular endothelial growth factor(VEGF)in neonatal rats after hypoxic-ischemic brain damage(HIBD).Methods The newborn rat HIBD models were prepared by Rice-Vannucci method and divided into control group(C),sham operation group(S),model group(M)and exercise training group(T).After 7 days of modeling,training was started for 1 week and 2 weeks.After taking brain tissue,the pathological changes of brain cells were observed by HE staining.The expression of BDNF and VEGF in brain tissue was detected by immunohistochemistry.The expression of miR-210 in brain tissue was detected by real-time quantitative fluorescent PCR.Results The brain tissue structure of group C and group S was clear,and the nerve cells showed degeneration and necrosis after modeling.The expressions of miR-210,BDNF and VEGF were significantly different between group T,group M and group S at each time point(P<0.05).The expressions of miR-210,BDNF and VEGF increased in the T group and M group over time.There were significant differences in the expression of the above indexes between the T and M groups at 14 d and 21 d(P<0.05).There was a significant positive correlation between VEGF expression and miR-210,BDNF(r=0.841,0.818,P<0.01).Conclusion Exercise training intervention in neonatal mice with hypoxic-ischemic brain damage can increase the expression of miR-210 and BDNF,and then promote the expression of VEGF in brain tissue,and finally protect the nerve injury.