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大鼠触液核丝裂原活化蛋白激酶磷酸酶1 (MKP-1)的分布及其在抑郁状态下的表达

陈萍, 林清松, 张励才

福建医科大学附属第一医院麻醉科；神经外科，福州 350000；徐州医学院江苏省麻醉学重点实验室，徐州 221009

摘要

本文旨在研究丝裂原活化蛋白激酶磷酸酶1 (MAP kinase phosphatase-1, MKP-1)在大鼠触液核(cerebrospinal fluid-contacting nucleus)的分布及其在抑郁状态下的表达变化，为探讨触液核的功能及其参与抑郁的调控机制提供实验依据。以Sprague-Dawley (SD)大鼠为实验动物，用慢性强迫游泳应激制作抑郁模型，用侧脑室注射辣根过氧化物酶标记的霍乱毒素B亚单位复合物(CB-HRP)特异性标记触液核神经元，用体重增长率、糖水偏好和旷场实验行为学指标来评价大鼠抑郁模型的建立，用免疫荧光双标法检测触液核MKP-1的分布，Image-Pro Plus计数目标神经元CB-HRP/fos和CB-HRP/MKP-1双阳性细胞的数目。结果显示，对照组大鼠触液核神经元有MKP-1分布；经过28天强迫游泳后，与对照组相比，应激组大鼠的体重增长率、糖水偏好、旷场得分明显降低，触液核中fos、MKP-1免疫阳性细胞数目明显增多，差异有统计学意义(P < 0.01)。以上结果显示，触液核可能参与抑郁症发病的调制，且通过MKP-1发挥重要作用。

关键词： 触液核; 丝裂原活化蛋白激酶磷酸酶1; fos; 慢性强迫游泳; 抑郁

分类号：R338

[The distribution of MAP kinase phosphatase-1 in the cerebrospinal fluid-contacting nucleus and its functional contribution to depressive behaviors.] [Article in Chinese]

CHEN Ping, LIN Qing-Song, ZHANG Li-Cai

Department of Anesthesiology； Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, Fuzhou 350000, China； Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou 221009, China

Abstract

The purpose of this research is to explore the distribution and expression of MAP kinase phosphatase-1 (MKP-1) in cerebrospinal fluid (CSF)-contacting nucleus in depression, and provide experimental evidence to reveal the biological function and regulatory mechanisms of CSF-contacting nucleus in depression. Depression model was produced by chronic forced swimming stress (CFSS) in Sprague-Dawley (SD) rats. Intracerebroventricular injection of cholera toxin subunit B (CTb) labeled with horseradish peroxidase (CB-HRP) was used to specifically mark distal CSF-contacting nucleus. The rate of animal growth and behavioral tests including sucrose preference test (SPT) and open field test (OFT) were used to validate the model of depression. The expressions of MKP-1 and fos proteins in CSF-contacting nucleus were detected by immunofluorescence. Software Image-Pro Plus version 6.0 was used to count the positive neurons. The results showed that, the distributions of MKP-1 were found in the CSF-contacting nucleus. After 28 days of swimming, the rats in stress group had a lower growth rate, a less consumption of sucrose and lower scores of OFT compared to control group. The number of neurons double labeled with CB-HRP/fos or CB-HRP/MKP-1 in stress group was significantly higher than that in control group (P < 0.01). These results suggest that the CSF-contacting nucleus may be involved in the process of depression via the MKP-1.

Key words: cerebrospinal fluid-contacting nucleus neurons; MAP kinase phosphatase-1; fos; chronic forced swimming stress; depression

收稿日期：2014-09-22　　录用日期：2014-12-10

通讯作者：张励才　　E-mail: lczhang@xzmc.edu.cn

引用本文：

陈萍, 林清松, 张励才. 大鼠触液核丝裂原活化蛋白激酶磷酸酶1 (MKP-1)的分布及其在抑郁状态下的表达[J]. 生理学报 2015; 67 (1): 90-96.

CHEN Ping, LIN Qing-Song, ZHANG Li-Cai. [The distribution of MAP kinase phosphatase-1 in the cerebrospinal fluid-contacting nucleus and its functional contribution to depressive behaviors.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (1): 90-96 (in Chinese with English abstract).