山西医科大学学报2024，Vol.55Issue(5)：594-603,10.DOI:10.13753/j.issn.1007-6611.2024.05.008
茶黄素通过抑制细胞过度自噬减轻新生大鼠缺氧缺血性脑损伤
Theaflavins alleviates hypoxic-ischemic brain damage in neonatal rats by inhibiting excessive autophagy
摘要
Abstract
Objective To investigate the role and mechanism of Theaflavins(TFs)in neonatal rats with hypoxic-ischemic brain damage(HIBD)based on silent information regulator 1(SIRT1)/forkhead box protein O1(FoxO1)signaling pathway.Methods Seven-day-old Sprague-Dawley(SD)rats were randomly divided into four groups:sham group,model group(HIBD group),TFs+HIBD group,and SIRT1 inhibitor group(TFs+HIBD+Ex-527 group),with 40 rats in each group.The rats in sham group only underwent dissociation of the right common carotid artery without ischemia or hypoxia treatment.The rats in model group underwent dissociation and ligation of the right common carotid artery by the modified Rice-Vannucci method and then hypoxia to establish the HIBD model.The rats in TFs+HIBD group and SIRT1 inhibitor group were given TFs orally before establishing the HIBD model,while the rats in SIRT1 inhibitor group were additionally injected with Ex-527 via lateral ventricle.Longa score,general condition,and behavioral testing were observed and evaluated,and brain tissue was weighed in the neonatal rats at 6,12,24,48,72 h after operation.The pathological changes of brain tissue were observed using HE staining.The expressions of SIRT1,FoxO1,Ac-FoxO1,Beclin1,and the ratio of LC3-Ⅱ/Ⅰ at the protein level were detected by Western blotting.Results Compared with sham group,the rats were lethargic,the neurological deficit score was significantly increased(P＜0.05),the increase of body mass was delayed(P＜0.01),the righting reflex time was signifi-cantly prolonged(P＜0.05),the mass of right brain tissue was increased(P＜0.05),the number of neurons in the cerebral cortex was decreased by HE staining,the levels of SIRT1 and FoxO1 were significantly decreased(P＜0.01),and the levels of Ac-FoxO1 and autophagy-related proteins(Beclin1 and LC3 Ⅱ/Ⅰ),were increased in HIBD group(P＜0.01).Compared with HIBD group,the mental state of neonatal rats was improved in TFs+HIBD group,the neurological deficit score was decreased(P＜0.05),the body mass gain was increased(P＜0.01),the righting reflex time was shortened(P＜0.05),and the mass of right brain tissue was decreased(P＜0.05),the number of neurons in the cerebral cortex was increased,the levels of SIRT1 and FoxO1 were increased(P＜0.01),and the levels of Ac-FoxO1 and autophagy-related were decreased in TFs+HIBD group(P＜0.01).Compared with TFs+HIBD group,the neurological deficit score was increased in TFs+HIBD group(P＜0.05),the increase of body mass was delayed(P＜0.01),the righting reflex time was prolonged(P＜0.05),and the mass of right brain tissue was increased(P＜0.05),the number of neurons in the cerebral cortex was decreased,the levels of SIRT1 and FoxO1 were decreased(P＜0.01),and the levels of Ac-FoxO1 and autophagy-related proteins were increased in TFs+HIBD group(P＜0.01).Conclusion TFs can inhibit the HIBD-induced excessive cell autophagy by activating SIRT1/FoxO1 signal transduction pathway,thereby reducing the neuronal cell injury.关键词
HIBD/TFs/SIRT1/FoxO1/细胞自噬Key words
hypoxic-ischemic brain damage(HIBD)/Theaflavins(TFs)/SIRT1/FoxO1/cellular autophagy分类
医药卫生引用本文复制引用
姜春玉,刘漠,王娇,李学斌,孙大中,张波,王显鹤..茶黄素通过抑制细胞过度自噬减轻新生大鼠缺氧缺血性脑损伤[J].山西医科大学学报,2024,55(5):594-603,10.基金项目
黑龙江省卫生健康委科研课题(20230202060379) （20230202060379）
黑龙江省创新训练项目国家级一般项目(202210222038) （202210222038）
