| 宋云飞.右美托咪定对减轻 APP/PS1小鼠海马区炎性因子分泌及细胞凋亡的作用[J].安徽医药,2021,25(2):238-242. |
| 右美托咪定对减轻 APP/PS1小鼠海马区炎性因子分泌及细胞凋亡的作用 |
| Anti inflammatory and anti apoptosis effects of dexmedetomidine on the hippocampus of APP/PS1 mice |
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| DOI：10.3969/j.issn.1009-6469.2021.02.006. |
| 中文关键词: 右美托咪定 阿尔茨海默病 早老素 1 细胞凋亡 内质网应激 淀粉样 β肽类 APP/PS1小鼠 内质网应激 海马神经元 |
| 英文关键词: Dexmedetomidine Alzheimer's disease Presenilin-1 Apoptosis Endoplasmic reticulum stress Amyloid betapeptides APP/PS1 mice ER-stress Hippocampal neurons |
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| 中文摘要: |
| 目的探讨右美托咪定( dexmedetomidine，DEX)对 APP/PS1转基因小鼠海马区抗炎抗凋亡的作用，并探讨其可能的机制。方法 2018年 3月至 2019年 3月，将 APP/PS1小鼠采用随机数字表法分为模型组( TG)、 DEX低、高剂量组( TG+10、20 μg/ kg DEX，每天腹腔注射 1次，连续 4周)和 4-苯基丁酸( PBA)阳性对照组( TG+400 mg/kg PBA，每天腹腔注射 1次，连续 4周)，另取野生型 C57BL/6小鼠作为对照组( WT)；水迷宫检测各组小鼠的学习与记忆能力； Nissl染色各组小鼠海马区神经细胞的数量； TUNEL检测各组小鼠海马区凋亡细胞数； ELISA检测各组小鼠海马区白细胞介素 -1β(IL-1β)、白细胞介素 -6(IL-6)及肿瘤坏死因子 α(TNF-α)蛋白的表达； WB法检测海马区 B淋巴细胞瘤 -2相关 X蛋白( Bax)、 B淋巴细胞瘤 -2(Bcl-2)和半胱氨酸天冬氨酸蛋白酶( caspase-3)的表达； WB法检测小鼠海马区内质网应激相关蛋白葡萄糖调节蛋白 78(GRP78)和内质网应激蛋白(CHOP)的表达。结果与 TG组比较， PBA和 DEX明显提高 APP/PS1小鼠的学习与记忆能力；增强海马区神经元的数量并减少神经细胞的凋亡；显著降低 IL-1β、IL-6及 TNF-α蛋白的浓度；抑制 Bax/Bcl-2和裂解的 caspase-3的表达；降低 GRP78和 CHOP的蛋白表达。结论 DEX对 APP/PS1小鼠海马区炎症因子分泌以及细胞凋亡有一定的减轻作用，可能是通过抑制海马区内质网应激来发挥治疗作用。 |
| 英文摘要: |
| Objective To investigate the anti-inflammatory and anti-apoptosis effects of dexmedetomidine (DEX) on the hippocampus of APP/PS1 transgenic mice and its possible mechanism.Methods APP/PS1 mice were randomly divided into four groups: model group (TG), low-dose and high-dose DEX group (TG+10, 20 μg/kg DEX, once a day, for 4 weeks) and PBA positive control group (TG+400 mg/kg PBA, once a day, for 4 weeks) from March 2018 to March 2019. Wild C57BL / 6 mice were used as control group (WT).Learning and memory abilities of mice in each group were tested by water maze. Nissl staining was used to detect the number of neurons in the hippocampus of mice in each group, the number of apoptotic cells in the hippocampus of mice in each group were detectedby TUNEL. The expression of IL-1β, IL-6 and TNF-α protein, Bax, Bcl-2, Caspase-3, GRP78 and CHOP were detected by WB, respectively.Results Compared with the TG group, PBA and DEX significantly improved the learning and memory ability of APP/PS1 mice;increased the number of neurons and reduced the apoptosis of neurons in the hippocampus; significantly reduced the concentration ofIL-1β, IL-6 and TNF-α protein; inhibited the radio of Bax/Bcl-2 and cleaved Caspase-3; decreased the protein expression of GRP78 and CHOP.Conclusion DEX can reduce the inflammatory factor release and apoptosis in the hippocampus of APP/PS1 mice, whichmay be due to the inhibition of ER stress in the hippocampus. |
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