Hepcidin对小鼠脑组织中铁沉积及运动行为能力的影响

Effects of hepcidin on brain iron deposition and exercise capacity of mice

目的:观察hepcidin对小鼠脑组织铁沉积及运动行为能力的影响,并探讨其作用机制。方法:将雌雄各半的昆明小鼠随机分为7组,分别为空白对照组、铁负荷组(2mg.ml-1、1mg.ml-1、0.5mg.ml-1)、hepcidin 5μg+铁负荷组(2mg.ml-1、1mg.ml-1、0.5mg.ml-1),以不同浓度的右旋糖酐铁隔日大腿肌肉注射建立铁过载模型。8周后,血细胞计数仪检测血液中血红蛋白含量,全自动生化分析仪检测血清铁含量,试剂盒检测血清中转铁蛋白(Tf)和总铁结合力(TIBC);原子吸收光谱法检测测定脑组织中铁的含量;ROS试剂盒检测脑组织中活性氧簇(Reactive oxygen species,ROS)含量;Morris水迷宫实验观察小鼠运动行为的改变。结果:与空白对照组比较,铁负荷组小鼠血清铁及血红蛋白含量明显增加,转铁蛋白(Tf)和总铁结合力(TIBC)明显减少,小脑、中脑和纹状体中铁含量和ROS明显升高,且呈剂量依赖性;Morris水迷宫实验结果显示,铁负荷组小鼠与空白对照组比较,平均逃逸时间明显增加,而靶象限活动时间明显下降(p<0.05);而hepcidin组均出现相反方向变化:hepcidin组小鼠平均逃逸时间明显下降,而靶象限活动时间明显增加。结论:铁过负荷对小鼠小脑、中脑和纹状体造成明显毒性损害,并引起脑的氧化应激,认知行为和空间记忆力下降;而hepcidin可抑制铁负荷引起的脑铁沉积和运动行为能力变化。

Objective： To observe the effect of hepcidin on deposit of mice brain iron and the exercise and behavior ability of mice, and discuss the mechanism. Methods： An equal number of male and female mice was randomly divided into seven groups： control goup, overload-iron group （2 mg·ml^-1, 1 mg·ml^-1, 0. 5 mg·ml^-1） and hepcidin group （5 μg） ＋ overload-iron group （2 mg·ml^-1 , 1 mg·ml^-1, 0. 5mg·ml^-1 ）. Intramuscular injection of iron dext-ran of different concentrations was given every other day for eight weeks to establish an iron-overload animal model. Blood hemoglobin content was tested by blood count instru-ment, serum iron content was tested by automatic biochemical analyzer, serum transferrin （Tf） and total iron binding capacity （TIBC） were detected using kit. The iron content of brain tissue was measured by atomic absorption spectrometry, and the ROS of brain tissue was measured by ROS kit. The Morris water maze tests were done respectively to observe the change of mice＇s move- ment behavior. Results： Compared with the control group, serum Fe and Hb increased significantly, Tf and TIBC significantly re-duced, Fe content in these brain areas including cerebellum, midbrain and striatum and ROS increased significantly in a dose-depend-ent manner. Morris water maze test results showed that, compared with control group, a significant increase in the average escape time and a significant decrease in target quadrant activity time were observed in overload-iron group. But the opposite results were observed in hepcidinq-overload-iron group. Conclusion： Iron overload of mice cerebellum, midbrain and striatum cause obvious toxic damage, leading to brain oxidative stress, cognitive behavior and spatial memory decline, but all these effects can be inhibited by hep-cidin.