慢性应激和舍曲林对大鼠前额叶皮质维生素D代谢的影响

摘要

目的 研究慢性不可预见性应激(CUMS)和舍曲林治疗对大鼠前额叶皮质维生素D(VD)代谢的影响.方法 雄性SD大鼠随机分为:正常对照组、正常对照+舍曲林组、抑郁模型组、抑郁模型+舍曲林组.正常对照+舍曲林组和抑郁模型+舍曲林组给予舍曲林8 mg·kg-1·d-1,正常对照组和抑郁模型组给予同容量0.9%氯化钠溶液;给药的同时,抑郁模型组,抑郁模型+舍曲林组开始给予应激,造模过程持续6周.测定4组大鼠体质量变化、糖水偏好及前额叶皮质CYP27B1,CYP24A1与VDR表达变化.结果 与正常对照组比较,抑郁模型组体质量增长率和糖水偏好度显著下降(P<0.01);与抑郁模型组比较,抑郁模型+舍曲林组糖水偏好度上升(P<0.05).与正常对照组比较,抑郁模型组大鼠前额叶皮质CYP27B1和CYP24A1的蛋白表达显著上升,VDR蛋白表达也上升(P<0.01);与抑郁模型组比较,抑郁模型+舍曲林组大鼠前额叶皮质CYP27B1和CYP24A1的蛋白表达显著下降,VDR蛋白表达显著下降(P<0.01或P<0.05).结论 慢性应激激活前额叶皮质VD信号通路,而舍曲林在改善抑郁样行为的同时缓解应激对VD信号系统的激活,提示VD信号通路可能与应激引起的抑郁有关.%Objective To explore the relationship between vitamin D and depression and the effects of chronic unpredictable mild stress (CUMS) plus sertraline on vitamin D metabolism in rat brain.Methods Male SD rats were randomly divided into normal control group,normal control + sertraline group,CUMS group and CUMS+sertraline group.CUMS was used to build the animal model of depression.After chronic exposure to CUMS or sertraline (8 mg·kg-1·d-1) for 6 weeks,behavioral response (sucrose preference test) and vitamin D metabolism in the prefrontal cortex were analyzed.Results Compared with normal control group,6 weeks of CUMS procedure induced the rats to a depression-like state,decreased weight and sucrose preference,and increased the expression of enzymes involved in vitamin D activation and catabolism (CYP27B1 and CYP24A1,respectively) and vitamin D receptor (VDR) in rat prefrontal cortex.As compared with CUMS group,CYP27B1,CYP24A1 and VDR were significantly decreased in CUMS+sertraline group (P<0.01 or P<0.05).Conclusion CUMS activates vitamin D signaling in the brain of the animal models of depression,while sertraline alleviates depressive behavior and relieves stress-induced activation of vitamin D signaling,indicating that vitamin D signaling may be involved in the stress-induced depression.