西酞普兰对慢性应激大鼠海马CA1和CA3区神经细胞B细胞淋巴瘤/白血病-2及Bcl相关蛋白表达与凋亡的影响

目的 探讨西酞普兰对慢性应激大鼠海马CA1、CA3神经细胞B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl相关蛋白(Bax)表达和凋亡的影响.方法 40只雄性Sprague-Dawley大鼠随机分为对照组、应激组(生理盐水灌胃)、处理1～3组分别以不同剂量(1 mg·kg-1·d-1、4 nag·kg-1·d-1、8 mg·kg-1·d-1)氢溴酸西酞普兰灌胃],每组8只.采用强迫游泳制造慢性应激模型,用大鼠悬尾实验、力竭实验进行行为学观察,免疫组织化学检测Bel-2、Bax表达水平.脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测细胞凋亡.尼康图像分析软件测量分析Bcl-2、Bax阳性表达、凋亡阳性细胞数量及积分吸光度值.结果 应激组静止不动时间(279±53)s]长于对照组(182±35)s]及处理1～3组(200±71)s,(159±59)s,(165±54)s];挣扎次数(20±3)次]少于对照组(24±3)次]及处理1～3组(37±16)次,(32±10)次,(24±4)次];力竭时间(38.3±5.1)min]长于对照组(22.9±1.8)min]、短于处理1～3组(54.4±2.9)min,(69.3±17.6)min,(46.4±4.0)min];差异均有统计学意义(P<0.05或0.01).与对照组比较,应激组CA1、CA3神经细胞Bcl-2表达变弱、Bax表达增强、凋亡细胞增多,差异均有统计学意义(P<0.05或0.01).与应激组比较,处理1～3组Bcl-2表达增强、Bax表达变弱、凋亡细胞减少,差异均有统计学意义(P<0.05或0.01).处理组1～3组的部分Bcl-2/Bax表达、凋亡阳性细胞数量与对照组的差异有统计学意义(P<0.05),但IA值的差异均无统计学意义(P均>0.05).结论 慢性应激可影响大鼠海马CAI、CA3神经细胞Bcl-2、Bax表达水平,促进细胞凋亡;西酞普兰可影响慢性应激大鼠海马CAI、CA3神经细胞Bcl-2、Bax表达水平,拈抗细胞凋亡.

Effects of citalopram on expression of B-cell lyraphoma/leukemia-2 and Bcl-associated X protein and neuron apoptosis in hippocmnpus CA1 and CA3 regions of long-term stress rats

Objective To explore effects of citalopram on preventing neuron apoptosis in CA1 and CA3 regions of hippocampus in chronic stress rats.Methods Forty male Sprague Dawley rats were randomly divided into five groups with eight each group.Stressed rat models were made by forced swimming daily for 4 weeks,and the stressed group wag treated with intragagtric administration of 0.9% sodium chloride,and three experimental groups with different dosage of citalopram.The fifth group was given no treatment as control.The proteins of bcl-2 and bax were detected with immunohistochemistry.Apoptosis cell number and integral optical density in CA1 and CA3 regions were tested and analyzed with terminal deoxynucleotidyl transferage biotin-dUTP nick end labeling(TUNEL)method and Nikon imaging software-BR(NIS-BR).Results The stationary time Wag longer in the stress group(279±53)s]than the control group(182 ±35)s],and the three citalopram treatment group(200±71)s,(159±59)s,(165±54)s].The number of struggling(20 ±3)times]was less than control group(24 ±3)times]and the treatment groups(37 ±16),(32 ±10),(24 ±4)times],and exhaustive time(38.3 ±5.1)min]longer than control group(22.9±1.8)min],shorter than treatment groups(54.4 ±2.9)min,(69.3±17.6)min,(46.4±4.0)min].AlJ tIle differences were statistically significant(P＜0.05 or 0.01).Rats in the stress group showed more apoptotic cells,reduced expression of bcl-2 and increased bax protein expression in CA1 and CA3 regions(P＜0.05 or 0.01)in comparison with control group.Compared to the stressed group,rats in treatment groups showed Iess apoptotic cells,reduced expression of bax and increased bcl-2 protein expression in CA1 and CA3 regions(P＜0.05).Conclusion Long-term stress might cause neuron apoptosis and expression of bcl-2 and bax in CA1 and CA3 region of hippocampus,and citalopram might have prophylactic effects on this process.