地塞米松PLGA磁性微球对炎性大鼠慢性疼痛的疗效评价

Effects of dexamethasone PLGA magnetic microspheres on chronic pain in inflammatory rats

目的 制备地塞米松聚乳酸-羟基乙酸共聚体(polylactic-co-glycolic acid, PLGA)磁性微球并对其治疗炎性大鼠慢性疼痛的疗效进行评价。方法 通过乳化-溶剂挥发法制备地塞米松PLGA磁性微球。采用完全弗氏佐剂注射于大鼠左后足足心进行建模。药效评价:将36只模型大鼠编号抽签随机分为6组,分别采取不同的处理方法,包括阳性对照组、磁疗组、地塞米松PLGA磁性微球组、地塞米松磷酸钠注射液组、地塞米松PLGA磁性微球+磁疗组、地塞米松磷酸钠注射液+磁疗组,每组6只。在建模后第2~10天观察大鼠左后足皮肤外观,并测试左后足足心机械痛阈,第10天在麻醉状态下取大鼠左后足足心局部皮肤病理行苏木精-伊红染色。结果 与各组大鼠治疗前机械痛阈比较,除了阳性对照组及磁疗组之外,其他组大鼠左后足足心机械痛阈在治疗后第4~6天均有明显改善(F=8.732,P=0.024),其中微球+磁疗组的改善最为明显。给药后第1~2天,微球+磁疗组与注射液+磁疗组的机械痛阈差异无统计学意义;而在第4~10天,微球+磁疗组的机械痛阈明显高于其他组。与阳性对照组比较,除磁疗组外,给药后第10天其余各组的炎性细胞均明显减少;地塞米松PLGA磁性微球组与地塞米松PLGA磁性微球+磁疗组改善程度最为明显。结论 地塞米松PLGA磁性微球有一定的缓释性和良好的生物相容性,对慢性炎症导致的慢性疼痛有明显改善作用。

Objective To prepare dexamethasone polylactic-co-glycolic acid(PLGA)magnetic microspheres and evaluate their therapeutic efficacy against chronic pain in inflammatory rats.Methods Dexamethasone PLGA magnetic microspheres were prepared using the emulsion-solvent evaporation method.Chronic pain models in rats were established by injecting complete Freund's adjuvant into the plantar surface of the left hind paw.Therapeutic efficacy was assessed in 36 model rats,which were randomly divided into six groups according to treatments:the positive control,magnetotherapy,dexamethasone PLGA magnetic microspheres,dexamethasone sodium phosphate injection,dexamethasone PLGA magnetic microspheres plus magnetotherapy,and dexamethasone sodium phosphate injection plus magnetotherapy,with six rats per group.The appearance of the rat's left hind paw skin and the mechanical pain threshold were observed from day 2 to day 10 post-modeling.On the 10th day,the left hind paw skin was pathologically examined under anesthesia using hematoxylin and eosin staining.Results After treatment,all groups except the positive control and magnetotherapy groups showed significant improvement in the mechanical pain threshold of the left hind paw between days 4 and 6 posttreatment,particularly in the microspheres plus magnetotherapy group.Inter-group comparisons revealed no significant difference in the mechanical pain threshold between the microspheres plus magnetotherapy group and the injection plus magnetotherapy group during the first two days post-administration.However,from day 4 to day 10,the microspheres plus magnetotherapy group showed significantly higher thresholds compared to the other groups. Except for the magnetotherapygroup, all the other groups showed a significant reduction in inflammatory cells compared to the positive control group onday 10 post-administration, espeically in the dexamethasone PLGA magnetic microspheres group and the microspheres plusmagnetotherapy group. Conclusion Dexamethasone PLGA magnetic microspheres exhibit sustained-release propertiesand good biocompatibility, which can significantly alleviate chronic pain caused by chronic inflammation.