目的 根据新药申报要求，研究聚乙二醇修饰重组人血管内皮抑制素（M2ES）对小鼠自主活动和协同睡眠的影响，以确定其可能关系到人安全性的非期望药理作用。方法 120只BALB/c小鼠，随机分为4组：对照组和M2ES低、中、高剂量组，分别单次尾iv氯化钠注射液和6、12、24 mg/kg的M2ES注射液。测定给药前和给药后15、60、120、240、360 min小鼠5 min内的自发活动次数，以及对阈下剂量戊巴比妥钠致小鼠睡眠的影响。结果 与对照组比较，M2ES低、中、高剂量组在给药前后各时间点小鼠的自主活动次数以及睡眠发生率均差异不显著。结论 M2ES在24 mg/kg及其以下剂量下对小鼠自主活动无显著性影响，与阈下催眠剂量的戊巴比妥钠无明显协同催眠作用。

Objective To investigate the effects of polyethylene glycol modified recombinant human endostatin (M2ES) on spontaneous activity and synergy sleep of BALB/c mice according to the requirement of new drug registration and application, and to assess the potential unexpected pharmacology effects on human. Methods Totally 120 BALB/c mice were divided into four groups: control group, M2ES low, medium, and high dose groups randomly, injected with sodium chloride injection and M2ES injection (6, 12, and 24 mg/kg), respectively. The number of spontaneous activity of the mice in 5 min before and 15, 60, 120, 240 and 360 min after treatment was determined, and the effects on hypnosis with pentobarbital sodium of subthreshold dose were also investigated. Results No significant difference in the number of spontaneous activity and sleep incidence between M2ES groups and control group in mice were observed. Conclusion M2ES has no significant effects on the spontaneous activity and hypnosis with pentobarbital sodium in mice at the dose of 24 mg/kg and below.

十二五“重大新药创制”科技重大专项（2012ZX09302001）