目的 根據(jù)新藥申報要求，研究聚乙二醇修飾重組人血管內(nèi)皮抑制素（M2ES）對小鼠自主活動和協(xié)同睡眠的影響，以確定其可能關(guān)系到人安全性的非期望藥理作用。方法 120只BALB/c小鼠，隨機分為4組：對照組和M2ES低、中、高劑量組，分別單次尾iv氯化鈉注射液和6、12、24 mg/kg的M2ES注射液。測定給藥前和給藥后15、60、120、240、360 min小鼠5 min內(nèi)的自發(fā)活動次數(shù)，以及對閾下劑量戊巴比妥鈉致小鼠睡眠的影響。結(jié)果 與對照組比較，M2ES低、中、高劑量組在給藥前后各時間點小鼠的自主活動次數(shù)以及睡眠發(fā)生率均差異不顯著。結(jié)論 M2ES在24 mg/kg及其以下劑量下對小鼠自主活動無顯著性影響，與閾下催眠劑量的戊巴比妥鈉無明顯協(xié)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“重大新藥創(chuàng)制”科技重大專項（2012ZX09302001）