外消旋聚乳酸/神经生长因子复合导管对失神经肌萎缩的早期作用

Precaution efficacy of poly-d,l lactic acid/neurotrophic growth factor compound conduit on denervated muscle atrophy

背景:前期实验已验证外消旋聚乳酸/神经生长因子复合导管对大鼠周围神经缺损再生确有促进作用,导管可在体内逐步降解。目的:探讨外消旋聚乳酸/神经生长因子复合导管中神经生长因子的释放在促进神经再生的同时能否有效防治肌萎缩,促进靶肌肉的功能恢复。设计、时间及地点:随机对照动物实验,于2006-04/2008-03在南方医科大学解剖学教研室实验室完成。材料:利用溶剂挥发法,制成内径1.5mm,壁厚0.3mm,长14mm的微孔单纯外消旋聚乳酸及外消旋聚乳酸/神经生长因子导管,每根复合导管含神经生长因子400U。方法:SD大鼠32只,随机分为单纯导管桥接组、复合导管桥接组,每组16只。制作右侧坐骨神经缺损模型,分别以单纯外消旋聚乳酸导管及外消旋聚乳酸/神经生长因子复合导管桥接修复,保留神经缺损10mm。主要观察指标:术后第5,10,15,20天大体观察右后肢肌肉萎缩程度及关节运动情况,测量三头肌湿质量恢复率,组织学观察肌细胞变化。并对小腿三头肌肌细胞直径和截面积进行量化分析比较。结果:所有大鼠术侧后肢跛行,小腿变细,随时间延长而加重。术侧小腿三头肌湿质量下降,恢复率随时间延长而降低,各时间段两组间比较差异均无显著性意义(P>0.05)。术后第5天术侧三头肌即开始萎缩变细,至第20天时肌细胞明显广泛萎缩,肌束间纤维组织增生。图像分析显示三头肌肌细胞直径和截面积随观察时间延长而进行性下降,4个时间段两组比较差异均无显著性意义(P>0.05)。结论:外消旋聚乳酸/神经生长因子复合导管局部释放神经生长因子对于早期(伤后20d内)失神经肌萎缩没有显著的抑制作用。

BACKGROUND： Previous research has shown that poly-d,I lactic acid （PDLLA）/neurotrophic growth factor （NGF） compound conduits could promote regeneration of ischemic peripheral nerves, while the conduits gradually degraded in vivo. OBJECTIVE： To determine whether the PDLLNNGF compound conduits could effectively prevent denervated muscle atrophy and promote functional recovery of target muscle at earlier period after promoting neural regeneration. DESIGN, TIME AND SETTING： A randomized and controlled animal experiment was performed at the Department of Anatomy, Southern Medical University from April 2006 to March 2008. MATERIALS： The pure PDLLA conduits and the PDLLA/NGF compound conduits were made with solvent-evolution method. Each conduit was with an internal diameter of 1.5 mm, a wall thickness of approximately 0.3 mm and a length of 14 mm. Each compound conduit contained 400U NGF. METHODS： A total of 32 SD rats were randomly divided into two groups on average： PDLLA group and PDLLA/NGF compound conduits group. The middle part of right sciatic nerve was excised and bridged with corresponding conduit. 10 mm nerve defect was retained in lumina of conduit. MAIN OUTCOME MEASURES： The precaution effect was evaluated according to the gross observation, triceps weight and histological indexes at day 5, 10, 15, and 20 postoperatively. Myocyte diameter and section area of triceps muscle of calf were quantitatively analyzed and contrasted between two groups at each stage. RESULTS： The right hindlimbs limped and showed thinningz in all rats after the operation. The recovery rate of triceps weight decreased gradually following the observation period lasted. There were no significant difference between PDLLA group and PDLLA/NGF compound conduits group at every stage （P 〉 0.05）. Normal muscle fiber of triceps appeared uniform shape and regulation alignment. But when it came to the 5th day after operation, the muscle fiber showed smaller diameter. General atrophy was apparent on the 20th day, various appearances, hclewglnouo vaccine sizes and fibroplasias around the muscle bundle. Image analysis showed that the myocyte diameter and section area of triceps reduced postoperatively, without significant difference between the two groups （P 〉 0.05）. CONCLUSION： The PDLLNNGF compound conduit has no significant depressant effect on denervated muscle atrophy at earlier period after bridging the sciatic nerve defect of rat （within 20 days after injury）.