文拉法辛对抑郁大鼠海马区神经元凋亡及相关凋亡因子表达的影响

Effect of venlafaxine on the hippocampus neuronal apoptosis in depressed rats and the expression of related apoptosis factors

目的研究文拉法辛对抑郁大鼠海马区神经元凋亡及相关凋亡因子表达的影响。方法将45只雌性SD大鼠随机分为对照组、模型组及实验组,每组各15只。模型组及实验组大鼠以慢性轻度不可见预见性应激(CUMS)结合孤养建立抑郁大鼠模型,共干预21 d。建模期间实验组灌服文拉法辛15mg·kg^(-1),每天1次,对照组及模型组则灌服等量生理盐水。糖水消耗试验评价各组大鼠行为学变化;用原位末端脱氧核苷酸转移酶标记法(TUNEL)染色检测各组大鼠海马区神经元凋亡情况;用蛋白免疫印迹法检测各组大鼠海马区凋亡相关因子表达情况。结果对照组、模型组及实验组糖水偏爱率分别为(69.94±1.95)%,(52.71±1.25)%,(66.23±0.98)%;海马区神经元凋亡数量(个/5个视野)分别为8.81±1.05,62.53±4.86,17.72±2.94。与对照组比较,模型组总液体消耗量、糖水消耗量、糖水偏爱率均显著降低,海马区神经元凋亡数量较对照组显著升高(P<0.01);而实验组糖水消耗实验各指标均较模型组升高,海马区神经元凋亡数量则较模型组显著降低(P<0.01);对照组、模型组及实验组海马区Bcl-xl蛋白相对表达量分别为1.43±0.03,0.79±0.02,0.97±0.02;Bcl-2相关X蛋白(Bax)相对表达量分别为0.43±0.02,0.96±0.03,0.57±0.02。与对照组比较,模型组海马区Bcl-xl蛋白相对表达量降低,Bax蛋白相对表达量升高(P<0.01);而与模型组比较,实验组海马区Bcl-xl蛋白相对表达量升高,Bax蛋白相对表达量降低(P<0.01)。结论文拉法辛可有效改善抑郁大鼠抑郁症状,抑制海马区神经元细胞凋亡,其作用机制可能与显著下调促凋亡因子Bax表达,上调抗凋亡因子Bcl-xl表达相关。

Objective To explore the effect of venlafaxine on the hippocampus neuronal apoptosis and the expression of related apoptosis factors of depressed rats. Methods Forfty-five rats were randomly divided into control group,model group and test group,15 cases in each group. Rats in model group and test group were built depressed rats model by chronic unpredictable mild stress（ CUMS） combined with solitary raise,intervened for 21 d continuously. The rats in test group were gavaged venlafaxine 15 mg·kg-（-1） during building model,1 time a day,and the rats in control group and model group were gavaged equivalent normal saline.The behavioral changes in each group were evaluated by sugar water consumption test; the hippocampus neuronal apoptosis in each group weredetected by terminal dexynucleotidyl transferase（ Td T）-mediated d UTP nick end labeling（ TUNEL）; the expression of hippocampus related apoptosis factors in each group were detected by Western blot（ WB）. Results The sugar water preferred rates in control group, model group and test group were（ 69. 94 ± 1. 95） %,（ 52. 71 ± 1. 25） %,（ 66. 23 ± 0. 98） %; the hippocampus neuronal apoptosis number（ number/5 views） were 8. 81 ± 1. 05,62. 53 ± 4. 86,17. 72 ± 2. 94. Compared with control group,the total consumption of liquid,sugar water consumption,sugar water preferred rate in model group decreased,the hippocampus neuronal apoptosis number in model group increased（ P〈0. 01）,the indexes of sugar water consumption test in test group increased compared with model group,the hippocampus neuronal apoptosis number in test group decreased compared with model group（ P〈0. 01）. The relative expression of hippocampus Bcl-xl protein in control group,model group and test group were 1. 43 ± 0. 03,0. 79 ± 0. 02,0. 97 ± 0. 02. The Bcl-2 associated X protein（ Bax） relative expression were 0. 43 ± 0. 02,0. 96 ± 0. 03,0. 57 ± 0. 02. Compared with control group,the hippocampus Bcl-xl protein relative expression in model group decreased,the Bax protein relative expression in model group increased（ P〈0. 01）; while compared with model group,the hippocampus Bcl-xl protein relative expression in test group increased,and the Bax protein relative expression in test group decreased（ P〈0. 01）. Conclusion Venlafaxine can improve the depressive symptom of depressed rat effectively,inhibit the hippocampus neuronal apoptosis,and the action mechanism maybe related to the down-regulation of pro-apoptotic factor Bax expression,and the up-regulation of anti-apoptotic factor Bcl-xl expression.