刺五加多糖调控SIRT1/PGC-1α通路对睡眠剥夺大鼠海马神经元损伤的影响  

Effect of Acanthopanax Senticosus Polysaccharides on Hippocampal Neuronal Damage in Rats with Sleep Deprivation by Regulating the SIRT1/PGC-1α Pathway

作　　者：代泓怡 狄岩 李翔[1] 岳思恩 DAI Hongyi;DI Yan;LI Xiang;YUE Sien(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《中医药导报》2025年第1期48-52,共5页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：北京慢性病防治与健康教育研究会科研项目(BJMB0012022028026)。

摘　　要：目的:探讨刺五加多糖对睡眠剥夺(SD)大鼠海马神经元损伤及沉默信息调节因子1(SIRT1)/过氧化物酶增殖激活受体γ协同激活因子1α(PGC-1α)通路的影响。方法:构建SD模型,并将其分为SD组、刺五加多糖低剂量组(ASP-L组)、刺五加多糖高剂量组(ASP-H组)、刺五加多糖高剂量+SIRT1抑制剂组(ASP-H+EX-527组),每组24只,另取24只正常大鼠作为对照组(Control组);酶联免疫吸附试验(ELISA)检测海马组织炎症及氧化应激反应相关因子水平;尼氏染色及苏木精-伊红(HE)染色观察海马组织病理学变化;原位末端转移酶标记技术(TUNEL)染色观察海马神经元的凋亡情况;透射电镜观察海马组织线粒体的超微结构;免疫印迹(Western blotting)检测SIRT1/PGC-1α通路相关蛋白表达。结果:SD组较Control组神经元排列紊乱,细胞间隙增宽,胞质内尼氏小体显著减少,核固缩深染,炎症细胞浸润明显,线粒体出现肿胀,嵴断裂,膜破裂,线粒体数量减少,长度缩短,TUNEL阳性率和肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、丙二醛(MDA)水平及Bcl-2相关X蛋白(Bax)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)表达升高,超氧化物歧化酶(SOD)活性及SIRT1、PGC-1α表达降低(P<0.05);ASP-L、ASP-H组较SD组神经元排列趋于整齐规则,细胞形态完整,尼氏小体数量增多,神经元炎性浸润及坏死等病理现象明显减轻,线粒体损伤减轻,TUNEL阳性率和TNF-α、IL-1β、MDA水平及Bax、Caspase-3表达降低,SOD活性及SIRT1、PGC-1α表达升高(P<0.05);ASP-H+EX-527组较ASP-H组神经元排列紊乱,尼氏小体数量明显减少,神经元损伤坏死严重,线粒体损伤加重,TUNEL阳性率和TNF-α、IL-1β、MDA水平及Bax、Caspase-3表达升高,SOD活性及SIRT1、PGC-1α表达降低(P<0.05)。结论:刺五加多糖可改善SD大鼠神经损伤,其可能与激活SIRT1/PGC-1α通路相关。Objective:To investigate the effects of Acanthopanax senticosus polysaccharides(ASP)on hippocampal neuronal damage and the silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor-γcoactivator-1α(/PGC-1α)pathway in rats with sleep deprivation(SD).Methods:The SD model was constructed and separated into SD group,low-dose Acanthopanax senticosus polysaccharides group(ASP-L group),high-dose Acanthopanax senticosus polysaccharides group(ASP-H group),and high-dose Acanthopanax senticosus polysaccharides+SIRT1 inhibitor group(ASP-H+EX-527 group),with 24 rats in each group.Another 24 normal rats were regarded as control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of inflammatory and oxidative stress-related factors in hippocampal tissue.Nissl staining and hematoxylin-eosin(HE)staining were applied to observe pathological changes in hippocampal tissue.In situ terminal transferase Labeling Technique(TUNEL)staining was applied to observe the apoptosis of hippocampal neurons. Transmission electron microscopy was applied to observe the ultrastructure of mitochondria in hippocampal tissue. Western blotting was applied to detect the expression of SIRT1/PGC-1α pathway related proteins. Results: Compared with the control group, the SD group showed disordered neuronal arrangement, widened intercellular gaps, greatly reduced intracellular Nissl bodies, deep staining of nuclear pyknosis, great infiltration of inflammatory cells, swelling, cristae rupture, membrane rupture, decreased number and length of mitochondria. And the positive rate of TUNEL, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA) and the expression of Bcl-2 associated X protein (Bax) and caspase-3 (Caspase-3) increased in SD group, while the superoxide dismutase (SOD) activity and expression of SIRT1 and PGC-1α decreased in SD group (P<0.05). The arrangement of neurons in the ASP-L group and ASP-H group tended to be neat and regular compared to the SD grou

关 键 词：刺五加多糖 沉默信息调节因子1/过氧化物酶增殖激活受体γ协同激活因子1α通路 睡眠剥夺 海马神经元损伤 大鼠 

分 类 号：R285.5[医药卫生—中药学]