中文摘要：

目的探讨鞘内注射新型镇痛药97-9-G4聚乳酸-聚乙醇胺共聚物（PLGA）缓释微球对慢性坐骨神经挤压（CCI）大鼠模型痛行为的影响。方法鞘内置管并成功制备右侧坐骨神经CCI模型SD大鼠。随机分为4组，每组8只：生理盐水组（NS），97-9-G4组（G组）；97-9-G4PLGA缓释微球组（SRG组），PLGA空白微球组（P组）。CCI造模后第11天起，连续3d，NS组和G组于7am、1pm和7pm分别3次鞘内给药，SRG组和P组分别于7am鞘内给药一次；于第14天，各组大鼠分别于8帅、12am、2pm、6pm和8pm5次测定机械痛阈和热辐射抬足潜伏期。结果微球平均粒径为77μm，药物包封率为80．4％，载药量约为27．78％。体外释放有2个释放高峰，其中前30min约有25．28％药物释放，在30min-24h时间段约有71．33％药物累积释放，体外释放至240h（10d）累积释放达98．3％。药物干预前各组大鼠机械痛阈和热辐射抬足潜伏期无统计学差异。给药后，G组在8am、2pm和8pm阈值较对照组（NS组）明显升高，有显著性统计学差异（P〈0．05）；12am和6pm组不存在显著性统计学差异（P〉0．05）；SRG组除8pm时间点外，同NS组比较均存在显著统计学差异（P〈0．05）；P组同NS组比较无统计学差异（P〉0．05）。结论97-9-G4PLGA缓释微球体外释放结果显示出良好的缓慢释放作用。动物实验提示鞘内注射该缓释制剂可以有效地对抗CCI模型引起的动物的机械痛敏和热痛敏，且作用时间可以持续约12h左右。

英文摘要：

Objective To study the pain killing effects of intrathecal injection of 97-9-G4 PLGA sustained-release microspheres in the SD rat model of CCI of sciatic nerve. Methods SD rats with intrathecal catheter deployment were randomly divided into 4 groups（n=8）： normal saline group（NS group）, 97-9-G4 group （G group）, 97-9-G4 PLGA sustained-release microspheres group（SRG group） and blank PLGA group（P group）. On the 1 lth day after CCI, the animals in NS group and G group were administered the relevant drugs three times （7 am, 1 pm and 7 pm; i.t.）. Those in SRG group and P group were administered only once （7 am; i.t.）. Paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL） were measured 5 times at the fixed time-point within the period of study. Results The drug entrapment efficiency was 80.4%, drug loading efficiency was 27.78%, and the mean diameter of microspheres was 77 wm. Two peaks of 97-9-G4 were observed in vitro release measurement. About 25.28% was released in the first 30 min and about 71.33% was accumulated released in the period from 30 min to 24 hours. Till 10 days, about 98.3% of 97-9-G4 was accumulated released from the microspheres. In vivo, compared with basic pain threshold, all groups, except sham group exhibited similar values of PWMT and PWTL at the beginning of drug administration. After drug administration, comparedwith NS group, the values of PWMT and PWTL were significantly increased at 8 am; 2 pm and 8 pm（P〈0.05）. At 12 am and 6 pm, there was no significant difference （P〉0.05）. Compared with NS group, the values of PWMT and PWTL in group SRG were significantly increased at all the time points except at 8 am. No significant difference was demonstrated in the values of group P as compared with group NS （P〉0.05）. Conclusion 97-9-G4 PLGA sustained-release microspheres demonstrate good appearance and significant in vitro sustained-release characteristics. In rat CCI models, the microspheres demonstrate good sustain