噻奈普汀对慢性应激大鼠海马N-乙酰天冬氨酸和胆碱复合物代谢水平的影响

摘要

Objective To explore the mechanism of stress-induced changes of behavior and hippocampal metabolites and the pharmacological action of tianeptine.Methods 24 rats were randomly allocated into control (n=6),4 week-stress(n=6),4 week-stress with saline(n=6) and 4 week-stress with tianeptine group(n=6),Forced Swimming Test(15min/d)was used to set up stress animal model.The stressful responses were assessed by behavior test and the concentration of serum corticosterone.The level of NAA/Cr and Cho/Cr of both side hippocampus in vivo was measured by 1H-MRS.Results Serum corticosterone level of control group is much lower than other groups (P＜0.01).The NAA/Cr level of left hippocampus of 4 week-stress with tianeptine group(1.287±0.061) and control group (1.304±0.088) is significantly higher than that of 4week-stress group(1.035±0.039) and 4 week-stress with saline group(1.020±0.085)(P＜0.01),but no difference was found between 4 week-stress with tianeptine group and control group,and between 4 week-stress group and 4 week-stress with saline group.In the right hippocampus,the NAA/Cr level of 4 week-stress with tianeptine group(1.278±0.080) and control group (1.268±0.070) is significantly higher than that of 4 week-stress group(1.015±0.049) and 4 week-stress with saline group(1.021±0.067)(P＜0.01),but no difference was found between 4 week-stress with tianeptine group and control group,and between 4 week-stress group and 4 week-stress with saline group.There is no difference of Cho/Cr value between 4 groups in both sides.Conclusion Chronic stress induced by forced swimming could result in the decrease of life vigor or cellular injury of hippocampus,and lead to the changes of hippocampal metabolisms.Stress-induced metabolic changes hippocampus may be prevented by tianeptine.%目的 探讨慢性应激对大鼠行为和在体海马代谢物浓度的影响以及噻奈普汀的药理作用.方法 将24只大鼠随机分成4组:对照组、4周应激组、4周应激加水组、4周应激用药组.采用强迫游泳试验,建立应激模型.应激后给予灌胃给药,4周应激组给予噻奈普汀50mg/kg,4周应激加水组按相同比例给予生理盐水.根据行为学和血清皮质酮水平评定应激效果,利用1H-MRS测量大鼠双侧海马N-乙酰天冬氨酸/肌酸(NAA/Cr)和胆碱复合物/肌酸(Cho/Cr)比值.结果 4周对照组皮质酮的水平明显低于其他组(P＜0.01),1H-MRS在体检测左侧海马NAA/Cr浓度4周应激用药组(1.287±0.061),对照组(1.304±0.088)明显高于4周应激组(1.035±0.039)和4周应激加水组(1.020±0.085)(P＜0.01),用药组和对照组差异无显著性,应激组和应激加水组差异无显著性.右侧海马NAA/Cr浓度4周应激用药组(1.278±0.080)和对照组(1.268±0.070)明显高于4周应激组(1.015±0.049)和4周应激加水组(1.021±0.067)(P＜0.01),用药组和对照组差异无显著性(P＞0.01),应激组和应激加水组差异无显著性(P＞0.01).双侧Cho/Cr值检测结果各组间均差异无显著性.结论 双侧海马在体NAA/Cr浓度降低提示,强迫游泳应激可以导致大鼠海马神经元生存活力的下降或结构破坏;噻奈普汀作为一种新型抗抑郁药可以对抗这一改变.