高铁对大鼠大脑皮层二价金属转运蛋白1表达的影响

Effect of high iron on the expression of divalent metal transporter 1 in the cerebral cortex of rats

目的探讨在脑铁代谢中发挥重要生理作用的二价金属转运蛋白1(DMT1)的表达及其调控机制。方法大鼠(n=6)侧脑室注射右旋糖酐铁3d和7d后,采用铁组织化学法检测脑内铁含量的变化,免疫组织化学技术检测大脑皮层中DMT1的两种亚型,即DMT1(+IRE)和DMT1(-IRE)蛋白表达的变化。结果铁组织化学染色结果显示,大鼠侧脑室注射右旋糖酐铁500μg/(只.d)7d后,大脑皮层中二价铁和三价铁均显著增高。同时,免疫组织化学结果表明,与对照组相比,脑内达高铁状态时大脑皮层DMT1(+IRE)蛋白表达显著升高,而DMT1(-IRE)蛋白表达无显著变化。结论在大鼠大脑皮层中,DMT1(+IRE)蛋白对铁水平的升高更为敏感,其表达与脑铁水平(尤其是二价铁)呈正相关。高铁对脑内不同区域内不同亚型DMT1表达的影响存在特异性。

Objective To investigate the effects of iron on the expression and regulation of divalent metal transporter 1 （DMT1） that may play an important role in the physiological brain iron metabolism. Methods Both the contents of ferric and ferrous iron as well as DMT1 （ ＋ IRE） and DMT1 （-IRE） protein expression were evaluated with iron histochemistry and immunohistochemistry in cerebral cortex （CC） after intracerebroventricular injection （ICV） of 500μg iron dextran/day for 3 or 7 days （each group contained 6 rats）. Results Iron histochemistry results showed that both the ferric and ferrous iron levels in CC were altered obviously after ICV for 7 days. Immunohistoehemistry results indicated that the expression of DMT1 （ ＋ IRE） in CC was not altered significantly after 3 days of ICV. Whereas the expression of DMT1 （ ＋ IRE） was increased significantly after 7 days of ICV when ferrous iron was increased significantly. Contrary to that of DMT1 （ ＋ IRE） expression in the same region, there were no significant alterations in DMT1 （ - IRE） expression in CC in spite of the existence of the altered brain iron levels, compared with that of control groups. Conclusion These data demonstrate that DMT1 （ ＋ IRE） expression is correlated primarily with brain iron levels; especially, its regulation is correlated positively with iron （ferrous iron） in adult rat CC, compared with those of saline- injected control rats. The effect of iron on the different isoforms of DMT1 expression may be different in different brain regions, but further investigations are needed to clarify these issues.