摘要
目的探究七氟烷对大鼠脑缺血再灌注损伤(CIRI)的影响及沉默信号调控因子1(SIRT1)自噬在其中发挥的作用。方法 SD大鼠分为假手术组、脑中动脉缺血(MCAO)模型组及七氟烷处理组(0.6%、1.2%、2.4%),不同浓度的七氟烷预处理大鼠, MCAO建模并进行神经功能评分,TTC染色检测脑梗死体积分数,并称量脑含水量,HE染色检测大脑皮质组织病理变化,TUNEL染色检测脑组织细胞凋亡,ELISA法检测脑组织肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白细胞介素10(IL-10)含量,RT-PCR检测SIRT1基因表达,Western blot检测SIRT1、微管相关蛋白1轻链3(LC3)、p62蛋白表达,自噬抑制剂3-MA和SIRT1 siRNA处理大鼠,检测其对大鼠CIRI损伤的影响。结果与假手术组比较,MCAO模型大鼠出现神经功能损伤,脑梗死体积分数增高,脑含水量增加,大脑皮质出现病理变化及细胞凋亡,组织炎症反应加重,SIRT1基因和蛋白表达升高,自噬水平提高;七氟烷预处理可减轻CIRI的病理损伤,同时使SIRT1表达和自噬水平进一步升高。3-MA抑制自噬和SIRT1沉默可扭转七氟烷在CIRI中的保护作用,同时降低自噬水平。结论七氟烷可通过诱导SIRT1依赖性自噬,减轻大鼠CIRI。
Objective To investigate the effect of sevoflurane on cerebral ischemia-reperfusion injury(CIRI) and the role of silent information regulator 1(SIRT1) as well as autophagy. Methods SD rats were divided into sham group, middle cerebral artery ischemia(MCAO) model group, sevoflurane(0.6%, 1.2%, 2.4%) treatment groups, rats were pretreated with different dose of sevoflurane, middle cerebral artery occlusion was used to establish model and neurological score was evaluated, the infarct volume was measured by TTC staining, and the brain water content was assessed, HE staining was used to detect the pathological change, cell apoptosis rate was measured by TUNEL assay, the contents of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), interleukin-10(IL-10) were measured by ELISA assay, SIRT1 gene expression was detected by RT-PCR, the protein levels of SIRT1,LC3 and p62 were detected by Western blot. Autophagy inhibitor 3-MA and SIRT1 siRNA were used to treat rats,and their effects on CIRI injury were examined. Results Compared with sham group,the MCAO model rats appeared neurological deficit,infarct volume rate increased,brain water content increased,significant pathological changes and apoptosis in the cerebral cortex appeared,inflammation increased,SIRT1 gene and protein expression increased,level of autophagy increased;sevoflurane pretreatment could alleviate the cerebral ischemiareperfusion injury,meanwhile,the SIRT1 expression and autophagy levels were further elevated. The autophagy inhibition of 3-MA and SIRT1 silence could reverse the protective effect of sevoflurane in cerebral ischemia-reperfusion,and decrease the level of autophagy. Conclusion Sevoflurane can attenuate cerebral ischemia-reperfusion injury in rats by inducing SIRT1-dependent autophagy.
作者
冉艳
卢明珊
曾德亮
张笃文
金宏玲
Ran Yan;Lu Mingshan;Zeng Deliang(Dept of Anesthesiology,People’s Hospital of Guizou Province,Guiyang 550002)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第1期103-109,共7页
Acta Universitatis Medicinalis Anhui
基金
贵州省科技厅-贵州省人民医院联合基金项目(编号:黔科合LH字[2015]7140号)。
关键词
七氟烷
脑缺血再灌注
自噬
沉默信号调控因子1
sevoflurane
cerebral ischemia-reperfusion
autophagy
silent information regulator 1
