促红细胞生成素在七氟醚麻醉诱发老龄大鼠海马神经细胞凋亡中的作用

发布时间：2018-08-03 14:37

【摘要】：目的探讨促红细胞生成素(erythropoietin,EPO)减轻七氟醚麻醉诱发老龄大鼠海马神经细胞凋亡的作用以及与Toll样受体4(toll like receptor 4,TLR4)的关系。方法雄性SD大鼠,20月龄,体重550~750g,根据随机数字表法将大鼠分为三组(n=9):对照组(C组),七氟醚处理组(S组)和EPO+七氟醚处理组(ES组)。S及ES组大鼠吸入4%七氟醚6h;C组仅吸入空气-氧气混合气体;ES组大鼠在七氟醚处理后24、48和72h行尾缘静脉注射EPO(5 000U/kg),C组和S组仅注射等量生理盐水。采用Morris水迷宫实验评价大鼠的认知能力,采用TUNEL法评价大鼠海马神经细胞凋亡率,采用RT-PCR法测定海马组织中TLR4mRNA表达,采用JC-1免疫荧光染色法检测海马神经细胞线粒体膜电位水平;采用免疫蛋白印迹法测定海马组织中淀粉样前体蛋白(APP)和β-淀粉样肽(Aβ)蛋白表达。结果与C组比较,S组逃避潜伏期明显延长,穿越平台次数差异无统计学意义,神经细胞凋亡率明显增加,TLR4mRNA表达明显下降,海马神经细胞线粒体膜电位水平明显下降,APP和Aβ表达明显增加(P0.05);与S组比较,ES组逃避潜伏期明显缩短,穿越平台次数差异无统计学意义,神经细胞凋亡率明显下降,TLR4 mRNA表达明显升高,海马神经细胞线粒体膜电位水平上升,APP和Aβ表达明显减少(P0.05)。结论促红细胞生成素能够减轻七氟醚诱发老龄大鼠海马区神经细胞的凋亡,其机制可能与抑制TLR4 mRNA表达,改善线粒体膜电位水平和抑制APP和Aβ蛋白活化相关。
[Abstract]:Objective to investigate the effect of erythropoietin (EPO) on the apoptosis of hippocampal neurons induced by sevoflurane anesthesia in aged rats and the relationship between erythropoietin and Toll like receptor 4 (toll like receptor 4 (TLR4). Methods male SD rats were 20 months old. The rats were randomly divided into three groups: control group (group C), sevoflurane treatment group (group S) and EPO sevoflurane treatment group (es group). S and es groups inhaled 4% sevoflurane for 6 hours. The caudal vein injection of EPO (5 000U/kg) in group C and group S was performed at 24 h 48 h and 72 h after sevoflurane treatment. The cognitive ability of rats was evaluated by Morris water maze test, the apoptosis rate of hippocampal neurons was evaluated by TUNEL method, and the expression of TLR4mRNA in hippocampus was measured by RT-PCR method. The level of mitochondrial membrane potential in hippocampal neurons was detected by JC-1 immunofluorescence staining, and the expression of amyloid precursor protein (APP) and 尾 -amyloid peptide (A 尾) protein in hippocampal tissue was detected by Western blot. Results compared with group C, the escape latency of group C was significantly prolonged, the number of times of crossing the platform was not significantly different, and the expression of TLR4 mRNA was significantly increased by the rate of neuronal apoptosis. The expression of app and A 尾 in hippocampal neurons decreased significantly (P 0.05), and the escape latency was significantly shorter in group S than in group S, and there was no significant difference in the number of times of crossing the platform between group S and group S, and the expression of app and A 尾 increased significantly (P 0.05). The expression of TLR4 mRNA was significantly increased and the expression of app and A 尾 were significantly decreased (P0.05). Conclusion Erythropoietin can attenuate the apoptosis of hippocampal neurons induced by sevoflurane in aged rats. The mechanism may be related to the inhibition of TLR4 mRNA expression, the improvement of mitochondrial membrane potential and the inhibition of APP and A 尾 protein activation.
【作者单位】：河北省安国市医院麻醉科;保定市第一医院麻醉科;解放军252医院麻醉科;定州市妇幼保健院麻醉科;定州市人民医院麻醉科;河北省安国市医院检验科;
【分类号】：R614

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