Protective effect of low-dose radiation on doxorubicin-induced brain injury in mice
Protective effect of low-dose radiation on doxorubicin-induced brain injury in mice
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DOI：
10.1016/j.abb.2022.109390
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发表时间：
2022-09-07
影响因子：
3.9
通讯作者：
Zhang，Shuang
中科院分区：
文献类型：
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作者：
Gao，Yan;Dong，Jingyao;Zhang，Shuang
方法60只雌性BALB/C小鼠随机分为对照组（CTR）、低剂量辐射组（LDR）、阿霉素治疗组（DOX）和阿霉素治疗前低剂量辐射组（COM）。在暴露于75 mGy 72小时后，向小鼠腹膜内注射7.5 mg/kg阿霉素，并在5天后处死。神经元特异性烯醇化酶（NSE），乳酸脱氢酶（LDH），三磷酸腺苷（ATP），神经递质，炎症介质，细胞凋亡和氧化应激相关介质以及线粒体功能障碍进行了检查。此外，与DOX组相比，COM组中促凋亡蛋白的表达下调。低剂量辐射提前减少活性氧自由基和激活SOD抗氧化防御系统，如显着减少GSH的表达，增加GSSG的表达，增加GPx的表达和激活Nrf 2氧化还原途径。低剂量辐射后，ATP 5 f1、NDUFV 1和CYC 1的表达水平接近正常，线粒体呼吸控制率（RCR）和呼吸链复合酶活性也趋于正常。低剂量辐射可上调IL-2和IL-4的表达，下调IL-10和TGF-β的表达。结论低剂量辐射对DOX所致小鼠脑损伤具有保护作用。其机制与LDR缓解线粒体功能障碍和氧化应激有关，促进抗氧化损伤蛋白的产生，从而对细胞发挥适应性保护作用。
BackgroundTo investigate the protective effect of low-dose radiation (LDR) on brain injury in mice induced by doxorubicin (DOX).MethodsSixty female BALB/C mice were randomly divided into the control (CTR) group, low-dose radiation (LDR) group, doxorubicin treatment (DOX) group and low-dose radiation before doxorubicin treatment (COM) group. After 72 hours of exposure to 75 mGy, the mice were intraperitoneally injected with 7.5 mg/kg of doxorubicin and sacrificed 5 days later. Neuron-specific enolase (NSE), lactate dehydrogenase (LDH), adenosine triphosphate (ATP), neurotransmitters, inflammatory mediators, apoptosis- and oxidative stress-related mediators as well as mitochondrial dysfunction were examined.ResultsCompared to the DOX group, the concentrations of DA, 5-HT, EPI and GABA in the COM group were significantly decreased, and the number of TUNEL-positive cells was decreased. In addition, the expression of proapoptotic proteins was downregulated in the COM group compared to the DOX group. Low-dose radiation in advance reduced reactive oxygen species and activated the SOD antioxidant defense system as indicated by significantly reduced GSH expression, increased GSSG expression, increased GPx expression and activation of the Nrf2 redox pathway. After low-dose radiation, the expression levels of ATP5f1, NDUFV1 and CYC1 were close to normal, and the mitochondrial respiratory control rate (RCR) and activity of respiratory chain complex enzymes also tended to be normal. Low-dose radiation upregulated the expression levels of IL-2 and IL-4 but downregulated the expression levels of IL-10 and TGF-β.ConclusionLDR has a protective effect on brain injury in mice treated with DOX. The mechanism is related to LDR alleviating mitochondrial dysfunction and oxidative stress, which promotes the production of antioxidant damage proteins, thus exerting an adaptive protective effect on cells.