摘要: |
目的 评价多肽药物酰米菲肽(XMT)的抗抑郁作用。方法 采用小鼠悬尾实验和小鼠强迫游泳实验研究XMT的抗抑郁作用,采用5-羟色氨酸(5-HTP)诱导小鼠甩头实验与小鼠育亨宾毒性增强实验探讨其可能的作用机制。结果 在小鼠悬尾实验中,采用XMT连续皮下注射5 d,其中0.3~10 mg/kg剂量范围的XMT可明显缩短悬尾不动时间,与生理盐水对照组相比差异有统计学意义(P<0.05);小鼠强迫游泳实验中,采用XMT连续皮下注射5 d,其中0.3~5.0 mg/kg剂量范围的XMT可明显缩短游泳不动时间,与生理盐水对照组相比差异有统计学意义(P<0.05)。以0.3~5.0 mg/kg作为XMT的有效剂量,未显示出中枢兴奋作用。给予小鼠连续5 d皮下注射0.3~10 mg/kg 剂量的XMT,其中5.0、1.0 mg/kg剂量可减少5-HTP诱导的小鼠甩头行为,与生理盐水对照组相比差异有统计学意义(P<0.01,P<0.05);而0.3~10 mg/kg剂量的XMT对育亨宾毒性均无明显增强作用,与生理盐水对照组相比差异无统计学意义(P>0.05)。结论 XMT在行为绝望动物抑郁模型上具有抗抑郁作用,其机制可能与拮抗5-羟色胺2受体(5-HT2受体)等多种途径相关。 |
关键词: 奈米菲肽 酰米菲肽 抗抑郁药 5-羟色胺 |
DOI:10.3724/SP.J.1008.2014.00539 |
投稿时间:2014-01-12修订日期:2014-05-08 |
基金项目: |
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Effects of a polypeptide drug—XMT on depression mouse models |
FU Xiao-fei1,XU Feng-hua1*,SU Huan-huan1,SONG Li-juan1,CHEN Jian2 |
(1. Department of Pharmaceutical Care, General Hospital of PLA, Beijing 100853, China; 2. Faculty of Pharmacy, Bengbu Medical College, Bengbu 233000, Anhui, China *Corresponding authors.) |
Abstract: |
Objective To study the antidepressant effect of a polypeptide drugs—XMT. Methods Using the suspension test, forced swim test, 5-hydroxy-L-tryptophan (5-HTP) induced head twitch response test and yohimbine induced lethality test in mice, the antidepressant effect and the possible mechanisms of XMT were measured. Results In the tail suspension test, repeated administration (0.3-10 mg/kg, sc) with XMT for 5 d reduced the immobility time in mice (P<0.05 vs the normal saline control). XMT (0.3-5.0 mg/kg, sc for 5 d) can reduced the immobility time in the forced swim test in mice (P<0.05 vs the normal saline control), while there was no central stimulated effect during the effective doses (0.3-5.0 mg/kg). Furthermore, XMT in repeated doses (5.0 and 1.0 mg/kg, sc for 5 d) decreased the 5-HTP induced head twitch response in mice (P<0.01, P<0.05 vs the normal saline control), while it had no effect on the yohimbine toxicity (P>0.05 vs the normal saline control). Conclusion XMT has antidepressant effect which may be related to the property of inhibition the 5-HT2 receptor, etc. |
Key words: nemifitide XMT antidepressant serotonin |