| 董晓荣,董继华,张瑞光,范丽,刘莉,张涛,伍钢.丹参酮ⅡA抑制电离辐射诱导胶质BV-2细胞激活的实验研究[J].中华放射医学与防护杂志,2010,30(5):535-539 |
| 丹参酮ⅡA抑制电离辐射诱导胶质BV-2细胞激活的实验研究 |
| Inhibitory effects of Tanshinone Ⅱ A on radiation-induced inflammatory response in microglia BV-2 cells |
| 投稿时间：2009-11-24 |
| DOI： |
| 中文关键词: 电离辐射 DNA双链断裂 小胶质细胞 炎性反应 丹参酮ⅡA |
| 英文关键词:Irradiation DNA double-strand break Microglia cells Inflammatory response Tanshinone ⅡA |
| 基金项目:国家自然科学基金(30800283) |
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| 中文摘要: |
| 目的 探讨丹参酮ⅡA能否抑制电离辐射诱导小胶质细胞激活及其机制。方法 用1.0 μg/ml丹参酮ⅡA处理小胶质细胞12 h,体外接受137Cs γ射线照射2、4、8、16和32 Gy后, 用实时PCR 检测致炎因子的变化,Western blot检测NF-κB p65表达的变化,免疫荧光染色及共聚焦显微镜检测γ-H2AX和p65的表达变化。结果 16和32 Gy照射后小胶质细胞激活,形态学上从静息状态下的小胞体多突起转变为放疗后胞体变圆和突起皱缩,并释放致炎因子IL-1β、TNF-α、IL-6、IFN-γ和COX-2与对照组相比,分别上调(5.0±0.60)、(2.1±0.20)、(2.4±0.25)、(1.6±0.30)和(3.6±0.50)倍(P<0.05)。丹参酮ⅡA能明显减少致炎细胞因子IL-1β、IL-6、IFN-γ和COX-2的释放,与对照组相比,分别为(2.3±0.10)、(1.8±0.20)、(0.3±0.30)、(0.2±0.10)(t=5.56,P<0.05)。Western blot分析提示,接受8和16 Gy电离辐射后,NF-κB的亚单位p65在细胞核的表达显著增加,而使用丹参酮ⅡA后可以减低电离辐射后p65在细胞核的表达;免疫荧光染色提示在未照射组p65表达于细胞质,电离辐射后p65转位至细胞核,而使用丹参酮ⅡA后可以抑制电离辐射后p65的核转位,使其表达于细胞质。结论 电离辐射后迅速引起一系列的分子内信号传导,通过DNA双链断裂(DSB)触发信号传导激活NF-κB信号通路;丹参酮ⅡA可以抑制电离辐射后NF-κB信号通路下调致炎因子表达,从而抑制小胶质细胞激活。 |
| 英文摘要: |
| Objective To explore the inhibitory effects of Tanshinone ⅡA on the radiation-induced microglia activation and the possible mechanism. Methods Microglia cells BV-2 were irradiated with 2, 4, 8, 16, and 32 Gy doses or sham-irradiated in presence or absence of 1.0 μg/ml Tanshinone ⅡA for 12 h,respectively. The effects of Tanshinone ⅡA on radiation-induced pro-inflammatory cytokines were evaluated using real-time PCR. The expression level of NF-κB p65 in cytoplasm and nucleus was measured by using Western blot. Immunofluorescence staining and confocal microscopy analysis were applied to detect the expression of γ-H2AX and p65 post-irradiation. Results The microglia cells were activated at 16, 32 Gy post-irradiation. Radiation-induced release of the pro-inflammatory cytokines in BV-2 cells was detectable after irradiation. Tanshinone ⅡA decreased radiation-induced release of pro-inflammatory cytokines(t=5.56, P<0.05). Furthermore, western blotting showed that Tanshinone ⅡA could attenuate the nuclear translocation of NF-κB p65 submit post-irradiation. Immunofluorescence staining showed that γ-H2AX foci formation while p65 translocation into nucleus post-irradiation. Conclusions Tanshinone ⅡA exerts anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes that might be associated with NF-κB signaling pathway. It is postulated that irradiation causes immediate cellular reaction and DSB triggers the molecular response which leads to NF-κB pathway activation. |
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