Genistein Alleviates Radiation-Induced Pneumonitis by Depressing Ape1/Ref-1 Expression to Down-regulate Inflammatory Cytokines
Genistein Alleviates Radiation-Induced Pneumonitis by Depressing Ape1/Ref-1 Expression to Down-regulate Inflammatory Cytokines
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金雀异黄素通过抑制 Ape1/Ref-1 表达下调炎症细胞因子来减轻辐射诱发的肺炎
DOI：
10.1007/s12013-014-9859-x
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发表时间：
2014-07-01
影响因子：
2.6
通讯作者：
Yang, Zhen-Zhou
中科院分区：
文献类型：
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作者：
Liu, Guo-Dong;Xia, Lei;Yang, Zhen-Zhou
该研究的目的是通过抑制脱嘌呤/脱嘧啶核酸内切酶 1/氧化还原因子-1 (Ape1/Ref-1) 的表达来下调炎症细胞因子水平，从而探讨金雀异黄酮在缓解放射性肺炎 (RIP) 方面的作用。将 50 只雌性 C57BL/6J 小鼠（8 周龄）随机分为对照组、纯照射（IR）组和金雀异黄素 + IR 组。 IR后4个时间点采用苏木精、Masson三色染色检查病理变化及胶原纤维沉积情况。流式细胞术用于检测活性氧系统（ROS）的变化，EMSA用于估计核因子κB（NF-κB）转录活性，ELISA测定用于测量IR后2周血清和支气管肺泡灌洗液（BALF）中TGF-β1、IL-1β、TNF-α和IL-6的水平。病理检测结果显示IR后胸组织出现急性炎症/纤维蛋白样渗出，金雀异黄素明显减轻。 IR 诱导的 APE1 蛋白表达增加，并且 NF-κB 被金雀异黄素有效抑制（P < 0.05）。 IR 诱导的炎症细胞因子 TGF-β1、IL-1β、TNF-α 和 IL-6 在经金雀异黄素预处理的小鼠的血清和 BALF 中依次受到抑制（P < 0.05）。此外，IR后A549细胞中ROS的产生显着增加，而金雀异黄素预处理可以下调ROS的产生。结果表明金雀异黄素通过减弱 RIP 启动时的炎症反应来减轻 RIP。金雀异黄素的一个可能靶点是 Ape1/ref-1，它通过激活 NF-κB 来调节关键的炎症细胞因子。
The aim of the study was to investigate the role of genistein in alleviating radiation-induced pneumonitis (RIP) through down-regulating levels of the inflammatory cytokines by inhibiting the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1). Fifty female C57BL/6J mice (8 weeks old) were randomly divided into a control group, a pure irradiation (IR) group and a genistein + IR group. At the four time points after IR, hematoxylin, and Masson’s trichrome stainings were used to examine the pathological changes and collagen fiber deposition. Flow cytometry was used to detect reactive oxygen system (ROS) changes, EMSA was used to estimate the nuclear factor kappa B (NF-κB) transcriptional activities and an ELISA assay was used to measure the levels of TGF-β1, IL-1β, TNF-α, and IL-6 in the serum and bronchoalveolar lavage fluid (BALF) 2 weeks after IR. The pathological detection results showed acute inflammatory/fibrinoid exudation of the thoracic tissue after IR, which was significantly alleviated with genistein. The IR-induced an APE1 protein expression increase and NF-κB was effectively suppressed by genistein (P< 0.05). The induction of the inflammatory cytokines TGF-β1, IL-1β, TNF-α, and IL-6 by IR were in turn inhibited in the serum and BALF of the genistein-pretreated mice (P< 0.05). In addition, the ROS production was significantly boosted in the A549 cells after IR, which could be down-regulated by the pretreatment of genistein. The results demonstrate that genistein alleviates RIP by attenuating the inflammatory response in the initiation of RIP. A possible target of genistein is the Ape1/ref-1, which regulates key inflammatory cytokines by activating the NF-κB.