目的研究亚慢性铝暴露对大鼠海马线粒体的损伤作用及其机制。方法无特定病原体级健康雄性成年SD大鼠60只,按体质量随机分为空白组、对照组和低、中、高剂量组,每组12只。空白组不作任何处理,低、中、高剂量组分别予剂量为0.41、0.81、1.62 mg/kg体质量的麦芽酚铝溶液,对照组予等体积0.9%氯化钠溶液,隔日腹腔注射染毒。连续染毒90 d后,以化学比色法检测大鼠海马组织中钠-钾-三磷酸腺苷酶(Na^+-K^+-ATP酶)和钙-镁ATP酶(Ca^2+-Mg^2+-ATP酶)活力,以免疫印迹法检测大鼠海马组织中细胞色素氧化酶4(CoxⅣ)、动力相关蛋白1(Drp1)、视神经萎缩蛋白1(Opa1)、线粒体融合蛋白(Mfn)1和Mfn2表达水平。结果高剂量组大鼠海马组织Na^+-K^+-ATP酶活力分别低于空白组、对照组和低剂量组(P〈0.05);中剂量组大鼠海马组织Ca^2+-Mg^2+-ATP酶活力低于空白组(P〈0.05),高剂量组大鼠海马组织Ca^2+-Mg^2+-ATP酶活力分别低于其他4组(P〈0.05)。中、高剂量组大鼠海马组织中CoxⅣ蛋白相对表达水平分别低于空白组、对照组和低剂量组(P〈0.05),Drp1和Mfn2相对表达水平分别高于空白组、对照组(P〈0.05),Opa1相对表达水平分别高于空白组、对照组和低剂量组(P〈0.05),Mnf1相对表达水平均高于空白组(P〈0.05)。结论麦芽酚铝亚慢性染毒可导致大鼠海马组织线粒体损伤,其造成的损伤可能与线粒体动力学的改变有关。
Objective To study effects and mechanism of sub-chronic aluminum-maltolate complex [Al( mal)3]exposure on mitochondrial damage of hippocampus in rats. Methods Sixty specific pathogen free healthy adult male SD rats were randomly divided into 5 groups: a blank group,a control group,a low-,a medium- and a high-dose group,with 12 rats in each group. Blank group was not treated. Low-,medium- and high-dose groups were treated with 0. 41,0. 81,1. 62 mg / kg body weigh of Al( mal)3solution respectively. The control group was treated with an equal volume of saline. Al( mal)3exposure was conducted by intraperitoneal injection every other day for 90 days. The activities of Na^+-K^+-ATPase and Ca^2+-Mg^2+-ATPase in hippocampus were tested by chemical colorimetric technique. Western blot analysis was used to detect the relative expression of cytochrome oxidase Ⅳ( Cox Ⅳ),dynamin-related protein 1( Drp1),optic Atrophy 1( Opa1),mitofusin( Mfn) 1,and Mfn2 in hippocampus. Results The activity of Na^+-k^+-ATPase in high-dose group was significantly lower than those in blank-,control-,and low-dose groups( P〈0. 05). The activity of Ca^2+-Mg^2+-ATPase in medium-dose group was significantly lower than those in blank group( P〈0. 05),and that in high-dose group was significantly lower than those in the other four groups( P〈0. 05). The relative expression levels of CoxⅣ in mediumand high-dose groups were lower than those of the other three groups( P〈0. 05). The relative expression levels of Drp1 and Mfn2 in medium-and high-dose groups were significantly higher than those in blank-,control and low dose group( P〈0. 05). The relative expression levels of Opa1 in medium- and high-dose groups were significantly higher than those in blank-,control- and low-dose groups( P〈0. 05). The relative expression levels of Mfn1 in medium- and high-groups were significantly higher than that in blank group( P〈0. 05). Conclusion The mitochondria of rat hippocampus