壳聚糖/聚乙二醇琥珀酸酯/丝裂霉素C释药系统预防椎板切除术后硬脊膜外瘢痕粘连的实验研究  

THERAPEUTIC EFFECTS OF CHITOSAN/POLYETHYLENE GLYCOLS-SUCCINATE/MITOMYCIN C FILM DRUG DELIVERY SYSTEM ON EPIDURAL SCARRING TISSUES AFTER LAMINECTOMY OF SD RATS

作　　者：张宇[1] 周初松[1] 蒋刚彪[2] 高飞[1] 傅栋[1] 

机构地区：[1]南方医科大学珠江医院骨科中心,广州510282 [2]华南农业大学资源环境学院制药工程系

出　　处：《中国修复重建外科杂志》2008年第10期1222-1226,共5页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：广东省科技计划资助项目(20042070019)~~

摘　　要：目的研究壳聚糖/聚乙二醇琥珀酸酯(chitosan/polyethylene glycols-succinate,CH/PEG-SA)/丝裂霉素C(mitomycin C,MMC)薄膜局部释药系统对硬脊膜外瘢痕粘连的治疗作用。方法按摩尔比3︰1制得PEG-SA后,将其与CH及MMC(质量比为1︰1.5)在一定条件下制成CH/PEG-SA/MMC薄膜。取成年雄性SD大鼠30只,制作L1椎板切除模型。将大鼠按体重编号,随机分为Ⅰ～Ⅵ组,每组5只。Ⅰ组硬脊膜后方植入20mgCH膜片,Ⅱ组植入20mgCH/PEG膜片,Ⅲ组植入20mgCH/PEG-SA膜片,Ⅳ组用0.05mg/mLMMC溶液浸润硬脊膜5min,Ⅴ组植入20mgCH/PEG-SA/MMC膜片,Ⅵ组不作处理。术后4周取材,通过大体观察(Rydell评分)比较硬脊膜外瘢痕的增生情况;行免疫组织化学观察,计算羟脯氨酸(hydroxyproline,Hyp)含量;HE染色行组织学观察。结果所有动物术后情况良好,无步态异常、躁动、感染、死亡,各组间Rydell评分比较差异均有统计学意义(P<0.05)。Ⅰ～Ⅵ组硬膜外瘢痕组织中Hyp含量分别为(0.5708±0.3450)、(0.7286±0.1506)、(0.5534±0.1223)、(0.3133±0.1064)、(0.2619±0.1021)及(1.0201±0.1206)μg/mg;Ⅰ～Ⅴ组Hyp含量均低于Ⅵ组,差异有统计学意义(P<0.05);Ⅳ、Ⅴ组与Ⅰ、Ⅱ、Ⅲ组比较,差异有统计学意义(P<0.05)。组织学观察见Ⅴ组胶原纤维少且与硬脊膜平行排列,走向清晰、规则,有少量炎性细胞浸润及毛细血管,无巨噬细胞反应。结论CH/PEG-SA/MMC膜片能有效减少硬脊膜外瘢痕中Hyp含量,抑制椎板切除术后硬脊膜外瘢痕粘连,是一种预防瘢痕粘连的良好辅助治疗手段。Objective To investigate the therapeutic effect of the chitosan/polyethylene glycols-succinate/ mitomycin C （CH/PEG-SA/MMC） film on epidural scarring tissues. Methods According to a specific proportion of respective materials, the film of CH/PEG-SA/MMC was developed under some condition. Thirty SD rats were selected and randomized into 6 groups with 5 rats in each group. A rat model of lumbar laminectomy was used. The amount of 20mg of the CH film was implanted into the animals in group Ⅰ, 20 mg of CH/PEG film in group Ⅱ, 20 mg of CH/PEG-SA film in group Ⅲ, 0.05 mg/mL of the MMC soaking for 5 minutes in group Ⅳ, 20 mg of CH/PEG-SA/MMC film in group Ⅴ, and nothing was done in group Ⅵ. Specimens were harvested 4 weeks after the above procedures and were then subjected to immunohistochemical and histological examinations to compare their therapeutic effects on epidural cicatricial tissues. Results All rats were in good conditions after operation, without gait abnormality, restlessness, infection and death. There was no significant difference among the 6 groups in the postoperative Rydell score （P 〈 0.05）. The content of hydroxyproline in groups I, Ⅱ, Ⅲ, Ⅳ, Ⅴ and VI was （0.570 8 ± 0.345 0）, （0.728 6 ± 0.150 6）, （0.553 4 ± 0.122 3）, （0.313 3 ± 0.106 4）, （0.261 9 ± 0.102 1）and （1.020 1 ± 0.120 6） μg/mg, respectively. There was a significant difference between groups Ⅳ, Ⅴ and groups Ⅰ, Ⅱ, Ⅲ （P 〈 0.05）, and there was significant difference between group VI and the rest 5 groups （P 〈 0.05）. According to the histological observation, group Ⅴ had less collagenous fiber paralleling the dura mater, with few inflammatory cells infiltration, with few capillary vessels and no reaction of macrophages. Conclusion CH/PEG-SA/MMC films can effectively reduce the amount of Hyp in epidural scarring tissues after lumbar laminectomy and therefore is a good treating method in preventing scarring tissue adhesion.

关 键 词：壳聚糖 聚乙二醇琥珀酸酯 丝裂霉素C 复合材料 局部药物释放系统 瘢痕粘连 

分 类 号：R687.3[医药卫生—骨科学]