Objective To investigate the antidepressant effects of histone deacetylase 6 (HDAC6) selective inhibitor tubacin for the model rats with chronic unpredictable mild stress (CUMS) and its mechanism.Methods Fifty male adult rats were randomly divided into 5 groups (n =10):control group (group A),CUMS model group (group B),Fluoxetine treat ment group (group C),tubacin treatment group (group D) and combination of Fluoxetine and tubacin treatment group (group E).The spatial learning and memory abilities of rats were tested by orientation navigation experiment and spatial probe trial of Morris water maze.Meanwhile,the levels of serum reduced glutathione (GSH) in all groups were measured by GSH kits.Results The orientation navigation experiment of Morris water maze showed that compared with group A,the mean escape latency of rats in group B was significantly lengthened (P ＜ 0.05 or P ＜ 0.01),compared with group B,the mean escape latency of rats in group C,D,E was significantly shortened (P ＜ 0.05 or P ＜ 0.01),and the mean escape latency of rats in group E was significantly shorter than those of group C,D (P ＜ 0.05 or P ＜ 0.01).In the spatial probe trial,the length of stay in the third quadrant of group C,D,E was significantly longer than those of the left three quadrants (P ＜ 0.05 or P ＜ 0.01),the length of stay in the third quadrant of group E was significantly longer than those of group C,D (P ＜ 0.01,P ＜ 0.05).The level of serum GSH in group B was significantly lower than that of group A (P ＜ 0.05),while the level of serum GSH in group C was significantly higher than that of group B (P ＜ 0.05),the level of serum GSH in group E was significantly higher than that of group C (P ＜ 0.05),there was no statistically significant difference between group E and group A (P ＞ 0.05).Correlation analysis showed that the spatial learning and memory abilities of rats were significantly correlated with the level of GSH (P ＜ 0.05).Conclusion HDAC6 selective inhibitor tubacin can improve the spatial learning and memory abilities of rats by regulating the levels of GSH,so as to play antidepressant effects.%目的 探讨组蛋白去乙酰化酶6(HDAC6)选择性抑制剂tubacin对慢性不可预见性温和应激(CUMS)模型大鼠的抗抑郁作用及其可能的作用机制.方法 将50只成年雄性SD大鼠随机分为五组(n=10):对照组(A组),CUMS模型组(B组),氟西汀处理组(C组),tubacin处理组(D组),氟西汀联合tubacin处理组(E组).应用Morris水迷宫定位航行试验及空间探索试验测试大鼠的空间学习、记忆情况.采用还原型谷胱甘肽(GSH)测定试剂盒检测各组大鼠血清中GSH水平.结果 Morris水迷宫定位航行试验显示,与A组比较,B组大鼠平均逃避潜伏期显著延长(P＜ 0.05或P＜ 0.01);与B组比较,C、D、E组平均逃避潜伏期明显缩短(P＜ 0.05或P＜0.01),且E组平均逃避潜伏期显著短于C组和D组(P＜ 0.05或P＜ 0.01).在空间探索试验中,C、D、E组大鼠在第三象限的停留时间明显长于其他三个象限(P＜ 0.05或P＜0.01),E组大鼠在第三象限的停留时间明显长于C组和D组(P＜0.05或P＜ 0.01).B组大鼠血清GSH水平明显低于A组(P＜0.05),C组血清GSH水平显著高于B组(P＜0.05),E组血清GSH水平较C组进一步提高(P＜0.05),并且与A组比较差异无统计学意义(P＞0.05).相关性分析发现,大鼠的空间学习、记忆能力与血清GSH水平显著相关(P＜0.05).结论 HDAC6选择性抑制剂tubacin可通过调节血清GSH水平以提高大鼠空间学习和记忆能力,从而发挥抗抑郁作用.
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