NRG1-ErbB4信号通路在氯胺酮抗抑郁中的作用

发布时间：2019-01-28 18:33

【摘要】：目的观察氯胺酮抗抑郁过程中大鼠海马神经调节蛋白-1(NRG1)、表皮生长因子4(ErbB4)及微清蛋白(PV)的变化,探讨NRG1-ErbB4信号通路在氯胺酮抗抑郁中的作用。方法雄性Wistar大鼠24只,200～250g,随机均分为四组(n=6):对照组(C组)、抑郁组(D组)、氯胺酮组(K组)及NRG1+氯胺酮组(N组)。N组大鼠行侧脑室置管。休息1周后,D、K、N组行强迫游泳15min建立大鼠抑郁模型。次日N组大鼠侧脑室给予NRG1;30min后,C、D、K、N组分别经腹腔注射生理盐水1ml、生理盐水1ml、氯胺酮10mg/kg、氯胺酮10mg/kg;给药后30min行强迫游泳实验,记录5min内不动时间。行为学测试后,取大鼠海马组织,采用ELISA法测定NRG1的含量,采用WesternBlot法检测ErbB4、p-ErbB4及PV蛋白水平。结果与C组比较,D组强迫游泳不动时间明显延长(P0.01),NRG1、p-ErbB4及PV表达明显上调(P0.05)。与D组比较,K组强迫游泳不动时间明显缩短(P0.01),NRG1、p-ErbB4及PV表达明显下调(P0.05或P0.01)。与K组比较,N组强迫游泳不动时间明显缩短(P0.05),NRG1、p-ErbB4及PV表达明显上调(P0.05或P0.01)。各组大鼠自主活动及ErbB4表达水平差异无统计学意义。结论 NRG1-ErbB4信号通路下调参与了氯胺酮的抗抑郁作用。
[Abstract]:Objective to observe the changes of neuroregulatory protein-1 (NRG1), epidermal growth factor 4 (ErbB4) and microalbumin (PV) in rat hippocampus during ketamine antidepressant, and to explore the role of NRG1-ErbB4 signaling pathway in ketamine antidepressant. Methods Twenty-four male Wistar rats were randomly divided into four groups: control group (C group), depression group (D group), ketamine group (K group) and NRG1 ketamine group (N group). N rats). After one week's rest, the depression model of rats was established by forced swimming 15min. The next day, the rats in group N were given NRG1;30min. The rats in group C were injected intraperitoneally with saline (1 ml), ketamine (10 mg / kg), and ketamine (10 mg / kg). After administration of 30min, forced swimming test was performed to record the time of immobility in 5min. After behavioral test, the content of NRG1 was measured by ELISA method, and ErbB4,p-ErbB4 and PV protein levels were detected by WesternBlot method. Results compared with group C, the immobility time of forced swimming in group D was significantly prolonged (P0.01), and the expression of NRG1,p-ErbB4 and PV were up-regulated (P0.05). Compared with group D, the immobility time of forced swimming in group K was significantly shortened (P0.01), the expression of NRG1,p-ErbB4 and PV was significantly decreased (P0.05 or P0.01). Compared with group K, the immobility time of forced swimming in group N was significantly shortened (P0.05), and the expression of NRG1,p-ErbB4 and PV were up-regulated (P0.05 or P0.01). There was no significant difference in autonomous activity and ErbB4 expression in each group. Conclusion the downregulation of NRG1-ErbB4 signaling pathway is involved in the antidepressant effect of ketamine.
【作者单位】：南京大学医学院临床学院南京军区南京总医院麻醉科;解放军第307医院麻醉科;
【基金】：国家自然科学基金(81271216) 全军“十二五”科研面上项目(CWS11J017)
【分类号】：R614

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