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脉络丛上皮铁调素表达的年龄变化与IL-6/Stat3信号途径

刘重斌, 王瑞, 董缪武, 高喜仁, 俞峰

湖州师范学院医学院基础医学系生理与药理教研室，湖州 313000；温州医科大学基础医学院生理教研室，温州 325000

摘要

老龄化可引起铁元素在脑内的蓄积。随着年龄的增加，脉络丛上皮可能是脑铁毒性、炎症反应和氧化应激损伤的重要结构。本文旨在研究铁代谢调节中的关键激素——铁调素在脉络丛上皮表达的年龄变化，及其与白细胞介素-6 (interleukin-6, IL-6)和信号转导子及转录激活子3 (signal transducer and activator of transcription 3, Stat3)的关系。本文以不同年龄段(3、6、9、12、15、18、21、24、27、30、33和36月龄)大鼠为研究对象，用实时定量RT-PCR和Western blot法检测铁调素及IL-6/Stat3信号途径相关蛋白在脉络丛上皮的表达变化。结果显示，3~18月龄年轻大鼠脉络丛上皮铁调素mRNA没有明显变化，21~36月龄大鼠的铁调素mRNA水平显著增加。脉络丛上皮IL-6和p-Stat3 mRNA和蛋白表达的年龄变化趋势与铁调素mRNA一致。以上结果提示，随着年龄的增加，炎症因子IL-6可能作用于相应的受体，通过Stat3信号转导途径，参与调节铁调素在脉络丛上皮的表达变化。

关键词： 老化; 脉络丛; 铁调素; 白细胞介素-6; 信号传导子及转录激活子3

分类号：R339.34

Expression of hepcidin at the choroid plexus in normal aging rats isassociated with IL-6/Stat3 signaling pathway

LIU Chong-Bin, WANG Rui, DONG Miao-Wu, GAO Xi-Ren, YU Feng

Department of Physiology, School of Medicine, Huzhou Normal College, Huzhou 313000, China； Department of Physiology, Wenzhou Medical University, Wenzhou 325000, China

Abstract

Accumulating evidence has revealed that brain iron concentrations increase with aging, and the choroid plexus (CP) may be at the basis of iron-mediated toxicity and the increase in inflammation and oxidative stress that occurs with aging. The mechanism involves not only hepcidin, the key hormone in iron metabolism, but also iron-related proteins and signaling-transduction molecules, such as IL-6 and signal transducer and activator of transcription 3 (Stat3). The aim of the present study was to investigate the correlation between the IL-6/Stat3 signaling pathway and hepcidin at the CP in normal aging. Quantitative real time PCR and Western blot were used to determine the alterations in specific mRNA and corresponding protein changes at the CP at ages of 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months in Brown-Norway/Fischer (B-N/F) rats. The results demonstrated that hepcidin mRNA level at the CP kept stable in young rats (from 3 to 18 months), and increased with aging (from 21 to 36 months). The alterations of IL-6/p-Stat3 mRNA and protein expressions in normal aging were in accordance with that of hepcidin mRNA. Our data suggest that IL-6 may regulate hepcidin expression at the CP, upon interaction with the cognate cellular receptor, and through the Stat3 signaling transduction pathway.

Key words: aging; choroid plexus; hepcidin; IL-6; Stat3

收稿日期：2014-03-23　　录用日期：2014-05-28

通讯作者：刘重斌　　E-mail: liuchongbin1972@126.com

引用本文：

刘重斌, 王瑞, 董缪武, 高喜仁, 俞峰. 脉络丛上皮铁调素表达的年龄变化与IL-6/Stat3信号途径[J]. 生理学报 2014; 66 (6): 639-646.

LIU Chong-Bin, WANG Rui, DONG Miao-Wu, GAO Xi-Ren, YU Feng. Expression of hepcidin at the choroid plexus in normal aging rats isassociated with IL-6/Stat3 signaling pathway. Acta Physiol Sin 2014; 66 (6): 639-646 (in Chinese with English abstract).