酰米菲肽对慢性应激模型大鼠的抗抑郁作用  

Antidepressant effect of a polypeptide drug-XMT on chronically unpredictably mildly stressed model rats

作　　者：付晓菲[1] 徐风华[1] 陈建[2] 宋立娟[1] 

机构地区：[1]解放军总医院,北京100853 [2]蚌埠医学院,安徽蚌埠233003

出　　处：《军事医学》2014年第4期281-284,293,共5页Military Medical Sciences

基　　金：国家科技重大专项资助项目(2012ZX09103301)

摘　　要：目的研究酰米菲肽(XMT)对慢性不可预见性轻度应激(CUMS)抑郁模型大鼠行为的影响,并探讨其可能的作用机制。方法 60只SD大鼠随机分为6组,分别为正常对照组、模型组、Flu阳性对照组(10 mg/kg)和XMT高、中、低剂量组(3.0、1.0、0.2 mg/kg)。除正常对照组外,其余采用CUMS+孤养的方法对大鼠持续应激刺激4周建立抑郁模型,造模成功后给予4周药物治疗。通过糖水偏好实验、旷场实验和体质量称量,观察动物的行为改变,采用酶联免疫法(ELISA)测定大鼠血清中促肾上腺皮质激素(ACTH)及皮质酮(CORT)含量。结果与正常对照组比较,各造模组大鼠经过应激刺激后糖水偏嗜度、自发活动和体质量增长均显著降低(P<0.05,P<0.01),血清ACTH和CORT水平显著升高(P<0.01),呈抑郁样表现。连续给予4周不同剂量的XMT能显著改善由慢性应激所致的大鼠抑郁样行为。与模型组比较,XMT治疗组大鼠的糖水偏嗜度、旷场水平得分及垂直得分、体质量增长显著升高(P<0.05,P<0.01),血清ACTH与CORT含量显著降低(P<0.05,P<0.01);与自身给药前数据比较,XMT(3.0、1.0、0.2 mg/kg)组大鼠给药治疗4周后的糖水偏嗜度显著增加(P<0.05),XMT(3.0、1.0 mg/kg)组大鼠旷场水平得分及垂直得分均显著增加(P<0.05)。结论 XMT对CUMS抑郁模型大鼠具有抗抑郁样作用,并可抑制慢性应激引起的下丘脑-垂体-肾上腺皮质轴(HPA)功能亢进。Objective To study the antidepressant effect of XMT on a chronically unpredictably mildly stressed （CUMS） depression model in rats and explore its possible mechanism. Methods Sixty male SD rats were randomly divided into six groups as follows： normal control, model, fluoxetine（Flu） positive control （10 mg/kg）, XMT of high, middle and low dosages （3.0, 1.0 and 0.2 mg/kg）. CUMS and solitary feeding condition were used to establish the rat depression model for 4 weeks, except in normal control group. Then all the rats were administered different drugs for 4 weeks. Sucrose preference test, open-field test and body mass change were measured to assess the behavioral efficacy. The levels of serum ACTH and CORT were determined by ELISA. Results After four weeks of stimulation, compared with normal control group, CUMS depression rats showed depression-like behavior, such as significantly lower sucrose preference, decreased crossing and rearing scores of open-field test, and reduced body mass （ P 〈 0. 05, P 〈 0. 01 ）. The concentration of blood serum ACTH and CORT increased obviously （P 〈 0. O1 ）. The treatment with XMT of high, middle and low dosages for 4 weeks could significantly reverse depression-like behaviors induced by CUMS. Compared with model group, the sucrose preference, crossing and rearing scores of open-field test, and body mass were increased obviously in XMT groups （P 〈 0. 05, P 〈 0.01 ） and the levels of serum ACTH and CORT were significantly improved（P 〈 0.05, P 〈0.01 ）. Compared with 4 weeks before, the sucrose preference of XMT （3.0, 1.0, 0.2 mg/kg） groups increased obviously （P 〈0.05）, so did the crossing and rearing scores of open-field test of XMT （3.0, 1.0 mg/kg） groups （ P 〈 0.05 ）. Conclusion XMT has antidepressant effect on the CUMS depression model in rats, which may be related to suppresing the hypothalamic-pitui- tary-adrenal axis.

关 键 词：酰米菲肽 抗抑郁药 下丘脑-垂体-肾上腺皮质轴 

分 类 号：R965[医药卫生—药理学]