丝裂霉素纤维蛋白凝胶缓释对硬膜外瘢痕粘连的实验研究  

Experimental study on the sustained release of mitomycin linked with fibrin gel for the prevention and treatment of epidural scar

作　　者：周磊[1] 蔡国栋[1] 王俊勤[1] 朱庄臣[1] 王增[1] 孔德谦 

机构地区：[1]泰山医学院附属医院骨科,山东泰安271000

出　　处：《中国矫形外科杂志》2013年第21期2200-2205,共6页Orthopedic Journal of China

基　　金：山东省泰安市科技局资助项目(编号:20093071)

摘　　要：[目的]探讨丝裂霉素C(mitomycinC,MMC)纤维蛋白凝胶(FG)缓释对脊柱硬膜外瘢痕粘连形成的预防作用。[方法](1)96只SD大鼠随机分为4组,每组24只,行L1椎板切除术,暴露硬脊膜,喷涂FG-MMC,根据术中应用MMC浓度不同分为4组,其中A组浓度为0.1 mg/ml;B组0.3 mg/ml;C组0.5 mg/ml;D组0.7 mg/ml。术后以每周为时间点,分别取各组手术节段的瘢痕组织,肉眼观察硬膜与周围组织粘连情况,并测定丝裂霉素的释药浓度,分析与时间的变化,选择MMC的最佳使用浓度;(2)48只SD大鼠建立L1椎板切除模型后随机分为4组,术中应用不同的防粘连材料,E组为丝裂霉素C(MMC);F组为纤维蛋白凝胶(FG);G组为MMC浓度为0.5 mg/ml的FG-MMC混合物;H组为生理盐水对照组。术后4周取材,评估硬膜与周围组织粘连程度;行HE和Masson染色;在550 nm波长下检测并计算瘢痕组织中羟脯氨酸浓度、推测胶原含量。[结果](1)A组硬脊膜与周围组织的粘连最重,C组粘连最轻。A、B、C、D组在第4周均出现药物释放高峰,其中C、D两组明显高于成纤维细胞50%抑制率质量浓度(ID50);对各组不同时间点的MMC浓度进行线性回归分析:C组F=924.415,P=0.000,有统计学意义;(2)E组与G组硬膜活动度良好,胶原增生不明显,HOP含量明显减少与对照组相比(P<0.05),具有统计学意义;F组与对照组相比无明显统计学意义(P>0.05)。[结论]FG-MMC缓释对预防大鼠椎板切除后硬膜外粘连具有较好的缓释作用,0.5 mg FG-MMC/ml浓度为最佳使用浓度。To study the sustained drug release of mitomycin C （MMC） linked with fibrin gel （FG） for the prevention and treatment of epidural scar adhesion after laminectomy. [ Methods ] （ 1 ） Ninety - six Sprague - Dawley （SD） rats underwent L1 - segment laminectomy and their spinal dura mater was exposed. Aftersurgery, FG - MMC was administered to prevent epidural scar adhesion. Sixty - four rats were randomized into 4 groups on the basis of the concentration of MMC adminis- tered： group A, 0. 1 mg/mL; group B, 0. 3 mg/mL; group C, 0. 5 mg/mL; and group D, 0. 7 mg/mL. Experimental sampling of the scar tissue in the laminoplasty segment was performed at weeks in 3 rats. The degree of dural adhesion in the laminoplasty segment was assessed by visual examination, and the MMC concentration in vivo inrats was determined. Subsequently, we calculated the most effective drug dose by plotting a dose - effect curve. （2） The 48 SD rats that underwent L1 - segment laminectomy were randomized into the following 4 treatment groups： group E （MMC）, group F （FG） , group G （FG- MMC, 0. 5mg/ mL）, group H （saline group） . Experimental sampling of the scar tissue in the laminoplasty segment was performed at 4 weeks after surgery. The degree of dural adhesion in the laminoplasty segment was assessed by visual examination, hematoxylin and eosin staining, and Masson staining, whereas collagen content was determined indirectly by detecting the concentration of hydroxyproline in the scar tissue. [ Results] （1） The degree of dural adhesion was most severe in group A and least severe in group C. In groups A, B, C, and D, the drug - release rate reached its peak after 4 weeks, and the 50% inhibition concentra-tion （IC50） for fibroblasts was significantly higher in groups C and D than in groups A and B. The concentration of MMC in each group at different time points was analyzed by the linear regression analysis （statistically significant for group C, F =924. 415, P = 0. 000） . （2） Compared to the

关 键 词：丝裂霉素 纤维蛋白凝胶 局部药物释放 瘢痕粘连 

分 类 号：R687.3[医药卫生—骨科学]