舒芬太尼调节AMPK/SIRT1/PGC-1α信号通路对新生大鼠缺血缺氧性脑损伤的保护作用  

Protective effect of sufentanil on ischemic hypoxic brain injury in neonatal rats by modulating AMPK/SIRT1/PGC-1αsignaling pathway

作　　者：王静[1] 唐玲[1] 肖婷[1] WANG Jing;TANG Ling;XIAO Ting(Department of Anesthesia and Surgery,Hunan Children’s Hospital,Changsha,Hunan 410007,China)

机构地区：[1]湖南省儿童医院麻醉手术科,湖南长沙410007

出　　处：《中国优生与遗传杂志》2023年第2期230-235,共6页Chinese Journal of Birth Health & Heredity

基　　金：2021年度湖南省卫生健康委科研立项课题(202104111245)。

摘　　要：目的探究舒芬太尼对新生大鼠缺血缺氧性脑损伤的保护作用及对AMP激活的蛋白激酶(AMPK)/沉默信息调节因子2相关酶1(SIRT1)/过氧化物酶体增殖物激活受体-γ共激活因子-1α(PGC-1α)信号通路的调节机制。方法将SPF级Wistar大鼠90只,随机分为假手术组、模型组、AMPK激活剂AICAR组、SUF低、高剂量组、SUF高剂量+AMPK抑制剂组。评估神经功能缺损评分;TTC染色法检测脑梗死情况;HE染色观察海马组织形态学变化;TUNEL法检测海马组织细胞凋亡率;ELISA测定血清肿瘤坏死因子-α(TNF-α)、脑源性神经营养因子(BDNF)、神经生长因子(NGF)水平;Western blot检测海马神经元AMPK、p-AMPK、SIRT1、PGC-1α蛋白表达水平。结果与假手术组相比,模型组大鼠海马组织可见细胞紊乱、坏死、肿胀等损伤,神经功能缺损评分、脑梗死面积、凋亡率、TNF-α水平均升高,BDNF、NGF水平及p-AMPK/AMPK、SIRT1、PGC-1α表达降低;与模型组相比,AICAR组和SUF低、高剂量组大鼠海马组织水肿等损伤减轻,神经功能缺损评分、脑梗死面积、凋亡率、TNF-α水平均降低,BDNF、NGF水平及p-AMPK/AMPK、SIRT1、PGC-1α表达升高;SUF高剂量+AMPK抑制剂组中AMPK抑制剂消除了SUF对上述指标的影响。结论舒芬太尼可能通过激活AMPK/SIRT1/PGC-1α信号通路保护新生大鼠免受缺血缺氧性脑损伤。Objective To explore the protective effect of sufentanil on ischemic hypoxic brain injury in neonatal rats and the regulatory mechanism of AMP-activated protein kinase(AMPK)/silent information regulator 2-related enzyme 1(SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC-1α)signaling pathway.Methods Ninety SPF Wistar male neonatal rats were randomly divided into sham operation group,model group,AMPK activator AICAR group,low-dose SUF,high-dose SUF group,high-dose SUF+AMPK inhibitor group.Neurological deficit scores were assessed.Cerebral infarction was detected by TTC staining,The morphological changes of hippocampus were observed by HE staining.The apoptosis rate of hippocampal tissue was detected by TUNEL method.The levels of tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and nerve growth factor(NGF)in serum were detected by ELISA.The protein expression levels of AMPK,p-AMPK,SIRT1,and PGC-1α in hippocampal neurons were detected by Western blot.Results Compared with the sham-operation group,the hippocampal tissue of the model group showed cell disorder,necrosis,swelling and other injuries,the neurological deficit score,cerebral infarction area,apoptosis rate,and TNF-α level increased,the BDNF,NGF levels,and the expression of p-AMPK/AMPK,SIRT1,PGC-1α decreased.Compared with the model group,the hippocampal tissue edema and other injuries of the AICAR group and the low-and high-dose SUF groups were alleviated,the neurological deficit score,cerebral infarction area,apoptosis rate,and TNF-α level decreased,the BDNF,NGF levels,and the expression of p-AMPK/AMPK,SIRT1,PGC-1α increased.In the SUF high-dose+AMPK inhibitor group,the AMPK inhibitor eliminated the effects of SUF on the above indicators.Conclusion Sufentanil may protect neonatal rats from hypoxic-ischemic brain injury by activating AMPK/SIRT1/PGC-1α signaling pathway.

关 键 词：舒芬太尼 AMPK/SIRT1/PGC-1α通路 新生大鼠 缺血缺氧 脑损伤 

分 类 号：R722.1[医药卫生—儿科]