硒对铝诱导小鼠脾脏氧化应激和炎症反应的颉颃作用

为探究硒对铝诱导小鼠脾脏氧化应激和炎症反应的颉颃作用机制，试验设4组：空白对照组、铝中毒组、硒对照组、硒＋铝组，各组小鼠灌胃给药处理4周后取脾脏组织。通过观察病理组织HE染色切片及免疫荧光染色切片来评价脾脏组织病理学变化；检测小鼠脾脏组织中谷胱甘肽过氧化物酶（GPx）活性及还原型谷胱甘肽（GSH）、丙二醛（MDA）、一氧化氮（NO）含量的变化；以实时荧光定量PCR检测脾脏组织中白细胞介素-1β（IL-1β）、IL-4、IL-6、干扰素-γ（IFN-γ）、血红素氧合酶1（HO-1）和NF-κB mRNA的表达水平；用Western blotting法检测脾脏组织中p-p65、IL-1β和HO-1蛋白表达水平。结果显示，铝处理后可使脾脏局部细胞间距增大，淋巴细胞减少，并伴有红细胞浸润，中性粒细胞增多，降低脾脏组织中GPx活性及NO和GSH的含量，导致MDA积累，IL-1β和NF-κB等炎症相关基因mRNA及蛋白表达水平升高，表现出对脾脏的氧化损伤和炎症反应；硒的加入可缓解铝的毒性作用，提高GPx活性及其他抗氧化物质的含量，降低脂质过氧化物MDA生成及炎症相关基因mRNA和蛋白的表达水平。本试验结果表明，铝能通过诱发小鼠氧化应激及炎症反应损伤脾脏，硒能缓解铝诱导的小鼠脾脏损伤，其机制可能与硒增强了脾脏的抗氧化水平有关。

Antagonistic Effect of Selenium on Aluminum-induced Oxidative Stress and Inflammation in the Spleen of Mice

To explore the molecular mechanisms of the antagonistic effect of selenium on aluminum-induced oxidative stress and inflammation in the spleen of mice,mice were divided into four groups as follows:Blank control group,aluminum group,selenium group,and selenium＋aluminum group.The spleen tissues of mice were taken 4 weeks after oral administration.Pathological changes of spleen were evaluated by HE staining and immunofluorescence staining of pathological tissue sections.Glutathione peroxidase (GPx),reduced glutathione (GSH),malondialdehyde (MDA) and nitric oxide (NO) levels were measured by respective commercial kits.IL-1β,IL-4,IL-6,IFN-γ,HO-1 and NF-κB mRNA expression levels were quantified by Real-time PCR,and p-p65,IL-1β and HO-1 proteins expression level were detected by Western blotting.The results showed that aluminum treatment could increase the local cell spacing of the spleen,decrease the number of lymphocytes,accompanied by an increase in neutrophils and red blood cell infiltration.Moreover,the activity of GPx and the content of NO and GSH were reduced,and the content of MDA was significantly increased.Likewise,the mRNA and proteins expression levels of inflammation-related such as IL-1β and NF-κB were increased,indicating oxidative damage and inflammatory reactions to the spleen.Selenium could alleviate the toxicity of aluminum,increase the activity of GPx and the content of other antioxidants,reduce the production of MDA and the expression of mRNA and protein of inflammation related genes.The results showed that aluminum could damage the spleen by inducing oxidative stress and inflammatory reaction in mice,and selenium could alleviate the spleen injury induced by aluminum.The mechanism might be related to selenium enhancing the antioxidant level of spleen and protecting spleen against tissue injury induced by oxidative stress and inflammatory reaction.