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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。
Objective To evaluate the antidepressant effect of the peptide drug acylfilippine (XMT). Methods The anti-depression effect of XMT was studied by mouse tail suspension test and forced swim in mice. The possible mechanism of 5-HTP-induced mouse head-shaving and mouse yohimbine-induced toxicity enhancement The mechanism of action. Results In mice tail suspension test, XMT was injected subcutaneously for 5 days. XMT 0.3 to 10 mg / kg significantly shortened the tail suspension time, which was significantly different from that of saline control group P <0.05). For forced swimming test in mice, XMT was injected subcutaneously for 5 days. XMT in the dose range of 0.3-5.0 mg / kg significantly shortened swimming immobility time, compared with the saline control group Significance (P <0.05). With 0.3 ~ 5.0 mg / kg as an effective dose of XMT, did not show the central excitement. The mice were injected subcutaneously with 0.3 ~ 10 mg / kg XMT for 5 days, and 5.0 and 1.0 mg / kg doses reduced the head-shaving behavior of mice induced by 5-HTP compared with the saline control group (P <0.01, P <0.05). However, 0.3 to 10 mg / kg XMT had no significant effect on the yohimbine toxicity, and there was no significant difference compared with the saline control group (P> 0.05). Conclusions XMT has antidepressant effect on depression model of behavioral desperation. Its mechanism may be related to the antagonism of 5-HT2 receptor (5-HT2 receptor) and other pathways.