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姜黄素对放线菌素D/TNF-α诱导的PC12细胞和大鼠海马神经元损伤的影响 被引量:7

Effects of curcumin on actinomycin D/TNF-α-induced injury in PC12 cells and rat hippocampal neurons
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摘要 目的:探讨姜黄素对放线菌素D(ActD)/TNF-α诱导的PC12细胞和大鼠海马神经元凋亡的影响及其作用机制。方法:将PC12细胞分为以下6组:对照组、TNF-α组、ActD组、姜黄素组、ActD/TNF-α组和姜黄素+ActD/TNF-α组。各组细胞培养24 h后进行下列处理:倒置荧光显微镜普通光观察各组细胞的形态变化;Annexin V/PI染色流式细胞术检测各组PC12细胞凋亡率;Fluo-3 AM染色流式细胞术测定细胞内Ca2+浓度。制备离体大鼠海马脑片,分组处理同PC12细胞,细胞外微电极记录技术观察各组海马脑片CA1区长时程增强(long-term potentiation,LTP)的变化情况。结果:10μg/L ActD和50μg/L TNF-α协同处理可导致PC12细胞明显损伤,而5μmol/L姜黄素则可以减轻这种损伤作用(P<0.05);ActD/TNF-α可诱导PC12细胞内Ca2+浓度升高,姜黄素可以通过降低胞内Ca2+浓度而减少ActD/TNF-α引起的细胞凋亡(P<0.05)。此外,LTP实验也证实ActD/TNF-α可以显著抑制大鼠海马脑片LTP的诱发,而姜黄素可以拮抗这种抑制作用,改善神经元突触可塑性(P<0.05)。结论:姜黄素可以改善ActD/TNF-α引起的神经元损伤,其机制可能是通过降低细胞内Ca2+浓度,维持胞内钙稳态而发挥作用。 AIM: To study the possible mechanism of cureumin on actinomycin D (ActD)/tumor necrosis factor ot (TNF-α) -induced injury in PC12 cells and rat hippocampal neurons. METHODS: PC12 cells wore divided into control group, TNF α group, ActD group, curcumin group, ActD/TNF - α group and curcumin + ActD/TNF - α group. The cells were cultured for 24 h. Inverted fluorescence microscopy was used to observe the morphological changes of the ceils in each group. Annexin V/PI double staining was applied to analyze the apoptosis of PC12 ceils. The level of intracellular Ca2+ was detected by Fluo -3 AM staining. Rat hippocampal slices were prepared and divided into the same groups as the PC12 cells. Extracellular microelectrode recording technique was used to observe and calculate the changes of long - term potentiation (LTP) in different groups. RESULTS: Apoptosis of PC12 ceils was induced by ActD/TNF-α. Curcumin protected the PCI2 cells from ActD/TNF- α- induced apoptosis (P 〈 0. 05). ActD/TNF-α increased the intracellular Ca2+ concentration. Curcumin significantly reduced ActD/TNF - α - induced apoptosis by decreasing the intraeellular Ca2+ concentration (P 〈 0. 05 ), inversed the effect of ActD/TNF -α on LTP in hippocampal slices, and improved the synaptic plasticity ( P 〈 0. 05 ). CONCLUSION: Curcumin protects ActD/TNF - α - induced neuronal damage by depressing the intracellular Ca2+ concentration and maintaining the homostasis of intracellular calcium.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2012年第10期1746-1750,共5页 Chinese Journal of Pathophysiology
基金 广东省自然科学基金资助项目(No.9151040701000) 国家重点基础研究发展计划(973)项目(No.2011CB707501) 广东省科技计划(No.2010B030700016) 广州市科技计划(No.2010Y1-C291) 国家自然科学基金资助项目(No.81171134)
关键词 姜黄素 肿瘤坏死因子 放线菌素D PC12细胞 细胞凋亡 Curcumin Tumor necrosis factor Actinomycin D PC12 cells Apoptosis
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