Neuroprotective effects of SMAds in a rat model of cerebral ischemia/reperfusion  

作　　者：Fang-fang Liu Chao-ying Liu Xiao-ping Li Sheng-zhe Zheng Qing-quan Li Qun Liu Lei Song 

机构地区：[1]Department of Neurology,First Hospital of Jilin University [2]Department of Respiratory Medicine,First Hospital of Jilin University [3]Department of Pediatrics,First Hospital of Jilin University [4]Department of Neurology,Affiliated Hospital of Yanbian University [5]Department of Hepatic-Biliary-Pancreatic Medicine,First Hospital of Jilin University

出　　处：《Neural Regeneration Research》2015年第3期438-444,共7页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81460193

摘　　要：Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phos- phorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor ne- crosis factor-a and interleukin-lβ mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflamma- tory and anti-apoptotic pathways.Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phos- phorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor ne- crosis factor-a and interleukin-lβ mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflamma- tory and anti-apoptotic pathways.

关 键 词：nerve regeneration brain injury NEUROPROTECTION inflammation apoptosis CEREBRALISCHEMIA SMAD3 transforming growth factor ~81 NSFC granl neural regeneration 

分 类 号：R743[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]