西酞普兰对应激大鼠额叶皮质神经细胞PCNA、C-fos表达及凋亡的影响

目的：研究西酞普兰对慢性应激大鼠额叶皮质神经细胞增殖细胞核抗原（PCNA）、原癌基因蛋白（C-fos）表达及凋亡的影响。方法：将24只健康雄性SD大鼠随机分为3组（n=8）：对照组（不做任何处理）、应激组（应激＋生理盐水灌胃）、实验组（应激＋西酞普兰灌胃），采用强迫游泳建立慢性应激模型，用免疫组化法检测PCNA、C-fos蛋白表达水平；TUNEL法检测细胞凋亡情况；尼康图像分析软件测量各指标阳性细胞数量。结果：应激组与对照组比较，可见少量PCNA表达阳性细胞、大量c-fos表达阳性细胞，阳性细胞的体积明显缩小。实验组与应激组比较，可见PCNA表达阳性细胞增多、C-fos表达阳性细胞明显减少，TUNEL阳性细胞数量减少，核浓缩现象较应激组明显减轻，染色也明显变淡，上述差异均有统计学意义（P〈0．05）。结论：慢性应激可影响大鼠额叶皮质神经细胞PCNA、C-fos蛋白表达水平，促进细胞凋亡，西酞普兰可调控额叶皮质神经细胞PCNA、C-fos蛋白表达水平，拮抗细胞凋亡，这可能是西酞普兰预防和治疗慢性应激引起的精神心理疾病的机制之一。

Effects of citalopram on the expression of PCNA and C-fos and cell apoptosis in rat frontal cortical neurons after stress

Objective： To study the effects of citalopram on the expression of proliferating cell nuclear antigen （PCNA）and pmto-onco- gene protein（C-fos） and cell apoptosis in frontal cortical neurons of rat after stress. Methods： Twenty four healthy male SD rats were randomly divided into three groups（ n = 8） ： control group, stress group（treated with saline, ig） , experimental group（treated with Citalopram 4 mg/kg · d for 28 days, ig）. Rats were forced to swim to establish chronic stress model. The protein expression levels of PCNA and C-fos were tested by immunohistochemistry assay. TUNEL assay was used to test cell apoptosis. Nikon image analysis software was used to determine the number of positive cells in each index. Results： Compared with the control group, the stress group showed a smaller amount of PCNA-positive cells, a larger number of C-fos positive cells, and the volume of positive cells was significantly reduced. Compared with the stress group , the PCNA positive cells were increased significantly, the C-fos positive cells and TUNEL positive cells were decreased significantly, nuclear condensation phenomenon in frontal cortical neurons and the staining was significantly lighter in experimental group （ P 〈 0.05）. Conclusion： Citalopram significantly antagonize PCNA, C-fos protein expression and cell apoptosis of rat prefrontal cortical neurons caused by chronic stress, which might be be the one of mechanisms of citalopram for prevention and treatment of psychosis caused by chronic stress.