万拉法新对强迫游泳大鼠下丘脑c-fos和c-jun蛋白表达的影响  

Effect of Venlafaxine on expression of c fos and c jun protein at the hypothalamus of forced swimming rats

作　　者：陆林[1] 黄明生[1] 李国君[2] 

机构地区：[1]华西医科大学附一院心理卫生研究所,成都610041 [2]华西医科大学公共卫生学院

出　　处：《临床精神医学杂志》1999年第5期257-260,共4页Journal of Clinical Psychiatry

摘　　要：目的：探索急慢性给予新一代抗抑郁药万拉法新对大鼠下丘脑ｃ－ｆｏｓ和ｃ－ｊｕｎ 蛋白表达的影响。　方法： 采用特性抗体的原位免疫细胞化学方法， 在强迫游泳大鼠抑郁模型上， 观察万拉法新急慢性给药对大鼠游泳不动时间和下丘脑核团ｃ－ｆｏｓ和ｃ－ｊｕｎ 表达的影响； 用图像分析技术对大鼠下丘脑室旁核（ＰＶＮ） 和视上核（ＳＯＮ） 内的ｆｏｓ和ｊｕｎ 阳性细胞的相对切面面积比和平均目标灰度进行分析。　结果：强迫游泳可使大鼠下丘脑内多个核团的ｃ－ｆｏｓ和ｃ－ｊｕｎ 蛋白表达水平增加，而万拉法新慢性给药明显缩短了强迫游泳大鼠的不动时间。图像分析提示： 万拉法新慢性给药使强迫游泳大鼠下丘脑ＰＶＮ和ＳＯＮ内ｆｏｓ和ｊｕｎ 阳性细胞相对切面面积比明显降低 （Ｐ＜ ０．０５）， 而平均目标灰度显著增加 （Ｐ＜０．０１）。　结论： 下丘脑ＰＶＮ和ＳＯＮ可能是介导抗抑郁药抑制大鼠绝望行为的重要中枢核团， 慢性给药对下丘脑ｃ－ｆｏｓ／ｃ－ｊｕｎ 蛋白表达的下调作用可能与临床上抗抑郁药疗效延迟现象有一定的关系。Objective:To study the effect of short and long term treatment of venlafaxine on the expression of c fos and c jun protein at the hypothalamus of forced swimming rats. Method:The distribution of c fos and c jun neurons within the hypothalamus of forced swimming rats was mapped with the immunohistochemical method during short and long term treatment with venlafaxine.The change in grey saturation and relative sectional area of FOS and JUN positive neurons at the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus was analysed with computerised imaging technique. Results:The expression of c fos and c jun protein could be induced by forced swimming and long term treatment with venlafaxine could suppress significantly the accumulated immobility time of forced swimming.The relative scctional area of fos and jun positive neurons was significantly decreased ( P <0 05) while grey saturation significantly increased ( P <0 01) during long term treatment with venlafaxine. Conclusion:The PVN and SON might be important structural substrates in the central nervous system mediation the action of antidepressants in despaired subjects like the forced swimming rats.The down regulation of c fos and c jun protein might be related with the delayed onset of action of antidepressants in the clinical setting.

关 键 词：抗抑郁药 万拉法新 强迫游泳 C-FOS C-JUN 

分 类 号：R971.4[医药卫生—药品]