噻奈普汀对慢性应激大鼠血清皮质酮和海马神经元增殖的影响

Effect of tianeptine on serum corticosterone and neuron proliferation in hippocampus of rats with chronic unpredictable stress

目的探讨慢性应激导致大鼠血清皮质酮浓度、海马神经元细胞增殖的改变以及噻奈普汀的抗抑郁机制。方法将24只大鼠采用抽签法随机分为：对照组、应激组、应激加水组、应激加药组（每组6只），均给予3周不可预料应激，应激加药组按50mg／kg给予噻奈普汀加0．9％氯化钠溶液灌胃，应激加水组按相同比例给予等量0．9％氯化钠溶液灌胃，采用酶联免疫吸附试验检测血清皮质酮浓度，Ki67免疫组化法测量海马齿状回细胞增殖。结果（1）应激前各组皮质酮的浓度差异无统计学意义，应激第1周对照组皮质酮浓度较其他各组低，差异有统计学意义（P〈0．01）；应激第2周对照组皮质酮浓度较其他各组低，差异有统计学意义（P〈0．01），应激加药组皮质酮浓度明显低于应激组和应激加水组，差异有统计学意义（P〈0．01）；应激第3周对照组和应激加药组皮质酮浓度明显低于其他两组，差异有统计学意义（P〈0．01）。（2）应激加药组大鼠海马的Ki67阳性细胞数明显高于应激组和应激加水组。差异有统计学意义（P〈0．01）。结论慢性不可预见应激可以导致皮质酮浓度升高及海马神经细胞增殖能力的下降，噻奈普汀可以预防或者逆转以上变化。

Objective To investigate the effect of tianeptine on serum corticosterone（CS）levels and neuron proliferation in the hippocampus of rats under chronic unpredictable stress. Methods Twenty four rats were randomly divided into control （n=6）, stress （n=6）, stress with saline （n=6） and stress with tianeptine （n=6） groups, chronic unpredictable stress（CUS） was used to set up stress model in rats. The serum corticosterone levels were measured by ELISA method and neuron proliferation in the hippocampus was examined by Ki67 immunohistochemical method. Results There were no significant differences in serum cor- ticosterone levels among all groups before stress. At the 1st and 2nd week of stress, serum corticosterone level in control group was significantly lower than that of other 3 groups （P〈0.01）; while the corticostrone level in tianeptine with stress group was lower than that of stress group and water with stress group（P〈0.01）. At the 3rd week, the serum corticosterone level in control group and tianeptine with stress group was significantly lower than that of stress group and water with stress group （P〈0.01）. The number of Ki67 positive cells in dentate gyrus （DG） of rat hippocampus in stress group and water with stress group was significantly less than that in tianeptine with stress group and control group（P〈0.01）. Conclusion Stress results in the increased of serum corticosterone concentration and decreased neuron proliferation in DG of hippocampus in rats, which may be prevented by tianeptine treatment.