首页|太白楤木总皂苷介导SIRT1/FOXO1/PGC-1α通路对创伤性脑损伤小鼠认知功能障碍的影响

太白楤木总皂苷介导SIRT1/FOXO1/PGC-1α通路对创伤性脑损伤小鼠认知功能障碍的影响

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目的 探讨太白楤木总皂苷(SAT)介导沉默信息调节因子1(silence infor-mation regulator 1,SIRT 1)/叉头转录因子1(forkhead transcription factor 1,FoxO1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)通路对创伤性脑损伤(trau-matic brain injury,TBI)小鼠认知功能障碍的影响.方法 将C57BL/6小鼠分为Con组、Model组、SAT组(135 mg·kg-1)、EX-527组(10 mg·kg-1 SIRT1抑制剂EX-527)、SAT+EX-527组,每组12只.Con组小鼠接受除皮层冲击外的所有手术操作,其余各组小鼠均利用可控皮层冲击法构建TBI模型,建模成功后,进行相应给药处理,每天1次,持续7 d.Morris水迷宫实验检测小鼠学习与空间记忆能力;HE染色检测损伤皮质病理学变化;ELISA法检测损伤皮质中白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)含量;TUNEL染色检测神经元凋亡;Western blot检测损伤皮质中半胱氨酸蛋白酶3(Caspase-3)、Bcl-2相关X蛋白(Bax)、SIRT1、Ace-FoxO1、Ace-PGC-1α蛋白表达.结果 与Con组比较,Model组小鼠脑皮层组织病理损伤严重,逃避潜伏期延长,穿越平台次数减少,损伤皮质中IL-6、TNF-α含量、神经元凋亡率、Caspase-3、Bax、Ace-FoxO1、Ace-PGC-1α蛋白表达升高,SIRT1蛋白表达降低(P<0.05);与Model组比较,SAT组小鼠脑皮层组织病理学损伤减轻,逃避潜伏期缩短,穿越平台次数增多,损伤皮质中IL-6、TNF-α含量、神经元凋亡率、Caspase-3、Bax、Ace-FoxO1、Ace-PGC-1α蛋白表达降低,SIRT1蛋白表达升高(P<0.05),而EX-527组对应指标变化呈相反趋势;EX-527逆转了 SAT对TBI小鼠认知功能障碍的改善作用.结论 SAT可能通过激活SIRT1/FoxO1/PGC-1α通路改善TBI小鼠认知功能障碍.
Effect of Total Saponin of Aralia taibaiensis on Cognitive Dysfunction in Mice with Traumatic Brain Injury by Mediαting SIRT1/FoxO1/PGC-1α Pathway
OBJECTIVE To investigate the effect of total saponin of Aralia taibaiensis(SAT)on cognitive dysfunction of mice with traumatic brain injury(TBI)by mediating silent information regulator 1(SIRT1)/forkhead transcription factor 1(FoxO1)/per-oxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)pathway.METHODS C57BL/6 mice were divided into Con group,model group,SAT group(135 mg·kg-1),EX-527 group(10 mg·kg-1 SIRT1 inhibitor EX-527),and SAT+EX-527 group,12 per group.Mice in the Con group received all surgical operations except cortical shock,and the controllable cortical shock method was used to construct the TBI model for the other groups.After the modeling was successful,the corresponding administration was performed,once a day for 7 d.Morris water maze test was performed to measure the learning and spatial memory abilities of mice;HE staining was performed to measure the pathological changes of damaged cortex;ELISA method was performed to measure the con-tents of interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α)in damaged cortex;TUNEL staining was performed to measure neu-ronal apoptosis;and Western blot was performed to measure the expressions of Caspase-3,Bcl-2 related X protein(Bax),SIRT1,Ace-FoxO1,and Ace-PGC-1α proteins in damaged cortex.RESULTS Compared with the Con group,the mice in the model group had severe pathological damage to the cerebral cortex,the escape latency was extended and the number of crossing platforms was re-duced,the levels of IL-6 and TNF-α,neuronal apoptosis rate,and the expressions of Caspase-3,Bax,Ace-FoxO1,and Ace-PGC-1αproteins in damaged cortex were increased,the expression of SIRT1 proteins was decreased(P<0.05).Compared with the model group,the pathological damage of the cerebral cortex of the mice in the SAT group was reduced,the escape latency was shortened and the number of crossing platforms was increased,the levels of IL-6 and TNF-α,neuronal apoptosis rate,and the expressions of Caspase-3,Bax,Ace-FoxO1,and Ace-PGC-1α proteins in damaged cortex were decreased,the expression of SIRT1 proteins was increased(P<0.05),the changes in the corresponding indicators of the EX-527 group showed an opposite trend.EX-527 reversed the improve-ment effect of SAT on cognitive dysfunction in TBI mice.CONCLUSION SAT may improve the cognitive dysfunction of TBI mice by activating the SIRT1/FoxO1/PGC-1α pathway.

total saponin of Aralia taibaiensistraumatic brain injuryapoptosisSIRT1/FoxO1/PGC-1α pathway

谭薇、吴莲珍、杨晨曦

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贵州中医药大学第一附属医院儿科,贵阳 550001

太白楤木总皂苷 创伤性脑损伤 细胞凋亡 沉默信息调节因子1/叉头转录因子1/过氧化物酶体增殖物激活受体γ辅激活因子1α通路

2024

中国药学杂志
中国药学会

中国药学杂志

CSTPCD北大核心
影响因子:0.957
ISSN:1001-2494
年,卷(期):2024.59(1)
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