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| 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 |
| Effect of erythropoietin attenuating apoptosis in old rat hippocampal neuronal cells exposed to sevoflurane: role of toll like receptor 4 |
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| DOI： |
| 中文关键词: Toll样受体 七氟醚 海马 细胞凋亡 神经毒性 |
| 英文关键词: Toll like receptor Sevoflurane Hippocampus Apoptosis Neurotoxicity |
| 基金项目: |
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| 摘要点击次数: 2796 |
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| 中文摘要: |
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550～750 g, 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6 h;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72 h行尾缘静脉注射EPO(5 000 U/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TLR4 mRNA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,TLR4 mRNA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(P<0.05);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(P<0.05)。
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。 |
| 英文摘要: |
Objective: To explore the effect of erythropoietin (EPO) attenuating apoptosis in old rat hippocampal neuronal cells exposed to sevoflurane and the role of toll like receptor 4.
Methods: Twenty months old SD rats, male, 550-750 g, in accordance with the random number table, were divided into 3 groups (n=9): control group (group C), sevoflurane treatment (group S), and sevoflurane plus EPO treatment (group ES). The rats in group S and ES were subjected to inhale 4% sevoflurane for 6 h, but the rats in group C were inhaled air-oxygen only. The rats in group ES were injected with EPO into caudal vein at 24 h, 48 h, and 72 h after sevoflurane exposure. The cognitive ability was assessed by Morris water maze test; the effects of hippocampal apoptosis were assessed by TUNEL assays; the expressions of TLR4 mRNA was measured by RT-PCR assay; mitochondrial membrane potential (MMP) was assessed by JC-1 fluorescence; the expressions of APP and Aβ were assessed by western blot.
Results: Compared with group C, there were significant increases of escape latency period, neuronal apoptosis, TLR4 mRNA, and APP and Aβ expression, but a decrease of MMP in group S (P<0.05). Compared with group S, there were significant decreases of escape latency period, neuronal apoptosis, TLR4 mRNA, and APP and Aβ expression, but a increase of MMP in group ES (P<0.05). br>Conclusion: The attenuation of rat hippocampal neuronal apoptosis induced by EPO could be associated with inhibition of TLR4, improvement of MMP, as well as inhibition of APP and Aβ activity. |
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