美洛昔康改善慢性应激大鼠抑郁行为的机制初探  

Effect of meloxicam on CUMS-induced depressive-like behavior in rats and its preliminary mechanism

作　　者：匡胜男 罗映[1] 田小燕[1] 张璐[1] 杨洋[1] 杨俊卿[1] 

机构地区：[1]重庆医科大学药理学教研室重庆市生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国药理学通报》2016年第2期263-268,共6页Chinese Pharmacological Bulletin

基　　金：重庆市科委项目(No cstc2012jj A0112)

摘　　要：目的初步探讨美洛昔康对慢性应激大鼠抑郁行为的影响及其机制。方法采用42 d慢性温和不可预知的刺激方法建立大鼠抑郁模型,美洛昔康(1、3 mg·kg^(-1))和舍曲林(5 mg·kg^(-1))在造模开始21d后灌胃给药,每天1次,连续21d。旷场实验和强迫游泳实验检测大鼠行为学变化,酶联免疫吸附法检测大鼠皮层PGE_2、TNF-α含量变化,高效液相色谱法(HPLC)分析大鼠皮层NE、DA、DOPAC、5-HIAA的含量变化,免疫组化法检测皮层5-HI1AR的表达变化。结果与正常组比较,慢性应激大鼠在旷场实验中水平和垂直运动减少(P<0.01),强迫游泳实验中静止不动时间延长(P<0.01),皮层中PGE_2、TNF-α含量增加(P<0.01),NE、DA、DOPAC、5-HIAA的含量明显减少(P<0.01),同时5-HT1AR(P<0.05)的表达减少。与模型组相比,美洛昔康能明显改善CUMS大鼠的抑郁行为,降低大鼠皮层PGE_2与TNF-α含量(P<0.01)的同时增加NE、DA、DOPAC和5-HIAA含量(P<0.05或P<0.01),上调5-HT1AR的表达(P<0.01)。结论美洛昔康能明显改善CUMS诱导的大鼠抑郁行为,其机制可能与其改善皮层炎症反应损伤,重建单胺递质系统平衡有关。Aim To explore the effect of meloxicam on the CUMS-induced depressive-like behaviors in rats and its preliminary mechanism.Methods The rats were exposed to CUMS procedure for 6 weeks to establish the model of depression.Meloxicam(1,3 mg ·kg^(-1)) and sertraline(5 mg · kg^(-1)) were administered to rats from 22 d of the stress procedure(once a day /or21 days,p.o.).Depressive-like behaviors were evaluated by the open-field test and force swimming test.The levels of PGE_2 and TNF-α in cortex were measured by ELISA.Moreover,the concentrations of NE,DA,DOPAC and 5-HIAA were also measured by HPLC,and the protein expression of 5-HT1 AR in cortex was analyzed by the immunohistochemistry.Results Compared with the rats of normal control group,the vertical and horizontal movement scores of rats in the open-field test were decreased and the immobility time in the forced swimming test was increased in model group.The levels of PGE_2 and TNF-α were both increased significantly,whereas the concentrations of NE,DA,DOPAC and 5-HIAA were decreased and the expression of 5-HT1 AR was reduced in cortex.Compared with the rats of model group,meloxicam significantly improved the depressive behaviors of rats in experimental groups and reversed the content of PGE_2,TNF-α,NE,DA,DOPAC and 5-HIAA,as well as the expression of 5-HT1 AR.Conclusion Meloxicam has a significant protective effect on CUMS-induced depressive-like behaviors,and the protective mechanism might be related to attenuating inflammation response and reconstructing the balance of the monoamine neurotransmitter system in rat cortex.

关 键 词：抑郁 CUMS 美洛昔康 炎症反应 细胞因子 5-HT1AR NE DA DOPAC 5-HIAA 

分 类 号：R-332[医药卫生] R322.81