摘要
目的观察4-苯基丁酸对创伤性脑损伤的保护作用及机制。方法将C57BL/6小鼠分为假手术组(Sham),创伤性脑损伤模型组(TBI)和4-PBA治疗组(4-PBA);TBI和4-PBA采用开放性脑刺伤方法建立TBI模型;观察并记录神经功能损伤评分;干湿法检测各组小鼠脑含水量;HE染色检测脑病理组织学变化;免疫荧光染色检测各组小鼠大脑皮层处胶质细胞的活化;TUNEL染色观察脑组织凋亡;Western blot检测GRP78、ATF-6、p-PERK的蛋白表达。结果4-PBA有效降低创伤性脑损伤小鼠神经功能评分,减少脑组织含水量,减轻脑损伤及炎性细胞浸润,大脑皮层的凋亡细胞百分比下降为21.05%±2.0%,同时下调GRP78、ATF-6、pPERK的表达。结论4-PBA可改善TBI小鼠脑组织损伤,其机制与抑制PERK信号通路有关。
Objective To observe the protective effect and mechanism of 4-Phenylbutyric acid(4-PBA)on Traumatic Brain Injury(TBI).Methods C57 BL/6 mice were divided into sham operation group(Sham),traumatic brain injury model group(TBI)and 4-PBA treatment group(4-PBA);TBI and 4-PBA were established by open brain injury method.The neurological impairment score was observed and recorded;the brain water content of each group was detected by dry and wet method.The histopathological changes of brain were detected by HE staining.The activation of glial cells in the cerebral cortex of each group was detected by immunofluorescence staining.The apoptosis of brain tissue was observed by TUNEL staining.The protein expression of GRP78,ATF-6 and p-PERK was detected by Western blot.Results 4-PBA effectively reduced the nerve function score of traumatic brain injury in mice and the brain water content,reduced brain injury and inflammatory cells infiltration,the apoptotic cells of the cerebral cortex percentage was 21.05%±2.0%,and down-regulated the expression levels of GRP78,ATF-6 and p-PERK.Conclusion 4-PBA improved brain tissue damage in TBI mice,which is related to inhibition of PERK signaling pathway.
作者
杨佳明
蒋玲
熊剑
李晓明
YANG Jia-ming;JIANG Ling;XIONG Jian;LI Xiao-ming(Department of Neurosurgery,General Hospital of Northern Theater,Shenyang 110016,China)
出处
《解剖科学进展》
2020年第5期559-562,566,共5页
Progress of Anatomical Sciences
基金
国家自然科学基金(81870890)
辽宁省自然基金(20170540935)。
