鞘内固体脂质纳米吗啡用于镇痛的实验研究

目的：观察大鼠鞘内单次注入固体脂质纳米吗啡（SLN-M）后的镇痛效应。 方法: SD雄性大鼠120只，随机分为3组。A组和B组为治疗组：A组分别按照1 μg、10 μg、25 μg、50 μg、100 μg的剂量鞘内给予普通吗啡，B组分别给予含1 μg、10 μg、25 μg、50 μg、100 μg吗啡的SLN-M；C组为对照组，鞘内分别给予生理盐水或SLN。用药后测定热痛阈值评价镇痛效果（以最大镇痛效应MPE表示），并对吗啡及SLN-M的50%有效镇痛剂量（ED50）进行计算分析，同时观察药物副作用。 结果: A组和B组动物鞘内给药后于30 min内达到最大强度的镇痛效应，A组镇痛持续时间明显短于B组（P<0.05），A组与B组动物给予不同剂量药物后的最大镇痛效应无明显差异（P>0.05），A组ED50为2.7 μg（95%可信区间：1.5-5.1 μg），明显低于B组的6.4 μg（95%可信区间：2.2-12.1 μg）（P<0.05），随用药剂量增加，A组不良反应发生率明显增加，并且显著高于B组（P<0.05）。结论: 鞘内单次给予SLN-M后通过持续缓慢释放吗啡发挥长时效镇痛作用，而且不良反应小于普通吗啡。

Effects of intrathecal solid lipid nanoparticles morphine on acute nociception in rats

AIM: To observe the effect of intrathecal injection of single dose solid lipid nanoparticles morphine (SLN-M) on acute nociceptoin in rats. METHODS: 120 male adult SD rats, weighing 220-280 g, were randomly divided into three groups. In group A, 10 randomly selected rats received single injection of intrathecal morphine at the following doses: 1 μg, 10 μg, 25 μg, 50 μg, or 100 μg. In group B, rats received the following doses of intrathecal SLN-M: 1 μg, 10 μg, 25 μg, 50 μg, or 100 μg; In group C, rats received saline or SLN without morphine, served as control group. The withdrawal latencies to radiant heat focused on plantar surface were measured as radiant heat threshold before and after intrathecal administration of the drug at the different time point. The percentage of maximal possible effect (MPE) was calculated. The 50% effective dose (ED50) values were determined for morphine and SLN-M by using analysis computer program. Behavioral and physiologic parameters were evaluated to assess side effects. RESULTS: The peak antinociceptive effect was observed within 30 min after intrathecal administration of morphine or SLN-M. Single dose of SLN-M resulted in equivalent analgesic efficiency and significantly prolonged analgesia compared with morphine hydrochloride. The ED50 was 2.7 μg (95% confidence interval: 1.5-5.1 μg) in group A, which was significant smaller than that in group B (6.4 μg, 2.2 μg-12.1 μg). Agitation or allodynia, rate of respiratory depression, catalepsy and loss of the corneal-reflex in group B were significantly higher than those in group A. CONCLUSION: Single intrathecal dose of SLN-M results in a restrained and persistent release of morphine from the intrathecal space. This extended release corresponded with an extended duration of analgesia and without an attendant increase in the incidence of side effects.