摘要
目的在新生大鼠缺氧缺血性脑病(HIE)发病的不同时期应用单磷酸腺苷激活的蛋白激酶(AMPK)激活剂5-氨基咪唑-甲酰胺核苷酸转甲酰酶(AICAR),观察其保护作用,探讨其作用机制。方法新生大鼠160只,分为假手术组、模型对照组、AICAR30 min组、AICAR24 h组和AICAR72 h组,各32只。采用Cresyl violet染色法比较手术后不同时间点(30 min,24 h,72 h)给予AICAR(500 mg·kg-1)对脑组织保护作用的差异;采用Foot-faults法评估大鼠远期预后;蛋白质印迹法检测脑组织中P-AMPK及三磷酸腺苷(ATP)的表达变化。结果假手术组与模型对照组大脑存活面积比例分别为(100.0±0.1)%和(45.3±6.3)%(P<0.05);手术后30 min、24 h给予AICAR治疗均有不同程度的保护作用,且手术后30 min治疗效果优于24 h(P<0.05),手术后72 h给予AICAR没有发现明显的保护作用(P>0.05)。早期给予AICAR治疗后可增加P-AMPK活性至假手术组约3倍,ATP含量可升至接近假手术组水平(P<0.05)。结论 HIE发病早期补充AICAR可调控AMPK信号通路,增加ATP含量,保护受损的神经元。
Objective To investigate the neuroprotective effects and mechanisms of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase / IMP cyclohydrolase(AICAR) supplement(AMPK activator) in different stages of neonatal rats sufferring from hypoxia-ischemia encephalopathy(HIE).Methods Neonatal rat hypoxia-ischemia brain injury model was employed in this study.A total of 160 neonatal rats were distributed into five groups:sham,model control,AICAR30 min,AICAR24 h and AICAR72 h.The neuroprotective effects of AICAR supplement(30 min,24 h,72 h post operation) were compared by cresyl violet staining;Expressions of P-AMPK,AMPK in the brain tissue were measured by Western blotting.Footfaults method was used to evaluate the long-term prognosis of the rats.Results Compared with the sham group,the survival of rats brain in model control group was significantly decreased [(100.0 ± 0.1) % and(45.3 ± 6.3) %,P < 0.05].AICAR had neuroprotective effects when treated at 30 min and 24 h post operation,while the protective effects disappeared when treated later(72 h post operation)(P>0.05).Compared with the sham group,the expression of P-AMPK significantly increased about three times,while ATP level decreased close to the same.Conclusion Early AICAR treatment can protect hypoxia-ischemia brain injury by increasing AMPK-ATP level.
出处
《医药导报》
CAS
2016年第9期943-946,共4页
Herald of Medicine
基金
第48批留学回国人员科研启动基金资助项目[(2014)1685]
湖北省自然科学基金资助项目(2013CFB085)
关键词
5-氨基咪唑-甲酰胺核苷酸转甲酰酶
单磷酸腺苷激活的蛋白激酶
脑病
缺血性
缺氧
神经元
5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase / IMP cyclohydrolase
Adenosine monophosphate activated protein kinase
Encephalopathy
hypoxia-ischemia
Neuron
