羧甲基壳聚糖-羧甲基纤维素膜对周围神经粘连形成及再生能力的影响*☆

背景：周围神经离断手术修复后吻合口粘连是影响神经功能恢复的主要因素。将有效的、可降解吸收的生物材料制成神经导管应用于吻合口，既能促进神经纤维的生长，又能预防吻合口周围粘连是目前研究的热点之一。 目的:评估羧甲基壳聚糖-羧甲基纤维素膜对周围神经粘连形成及再生能力的影响。 设计、时间及地点：随机对照动物实验，于2007-06/2008-06在解放军第二军医大学动物实验室完成。 材料：羧甲基壳聚糖-羧甲基纤维素膜(上海其胜生物材料有限公司研制，国家发明专利，专利号：ZL200410093448.9)； DIKFILM®聚-DL-乳酸可吸收医用膜(成都迪康中科生物医学材料有限公司生产)。 方法:60只大鼠随机分为3组，DIKFILM®膜组、羧甲基壳聚糖-羧甲基纤维素膜组和对照组，每组20只。切断坐骨神经直接端端吻合，对照组在神经吻合口处不作任何处理，另外2组用DIKFILM®膜、羧甲基壳聚糖-羧甲基纤维素膜分别包裹神经吻合口远近端各1 cm，并在薄膜中间缝合数针，使薄膜形成一个封闭的导管。 主要观察指标：术后12周观察神经再生和神经周围粘连形成情况。 结果:羧甲基壳聚糖-羧甲基纤维素膜组和DIKFILM®膜组神经吻合口周围的粘连程度及神经瘤的形成显著少于对照组，而且肢体功能恢复比对照组快。组织学检查羧甲基壳聚糖-羧甲基纤维素膜组和DIKFILM®膜组神经内及神经外纤维化明显比对照组低。羧甲基壳聚糖-羧甲基纤维素膜组和DIKFILM®膜组差异无显著性意义。术后12周3组大鼠手术肢体神经传导速度及动作电位波幅较术后4，8周增加(P < 0.05)；羧甲基壳聚糖-羧甲基纤维素膜组和DIKFILM®膜组神经传导速度较对照组快，动作电位波幅较对照组高(P < 0.05)。 结论:羧甲基壳聚糖-羧甲基纤维素膜能有效预防吻合口神经瘤的形成，并能促进神经纤维的再生。 关键词：羧甲基壳聚糖-羧甲基纤维素；膜；粘连；神经

Effects of carboxymethylchitosan-carboxymethylcellulose membrane on extraneural adhesion formation and peripheral nerve regeneration

BACKGROUND: Extraneural adhesion formation is the major problem interfere functional rehabilitation after peripheral nerve denervation. Therefore, the research regarding application of biomaterial nerve conduit in anastomotic stoma that can promote nerve regeneration, as well as prevent neuroma formation arouses more and more attention. OBJECTIVE: To evaluate effects of carboxymethylchitosan (CMCH)-carboxymethylcellulose (CMC) membrane on extraneural adhesion formation and peripheral nerve regeneration. DESIGN, TIME AND SETTING: A randomized control experiment was performed at the Animal Laboratory of Second Military Medical University of Chinese PLA from June 2007 to June 2008. MATERIALS: CMCH-CMC membranes were purchased from Shanghai Qisheng Biological Preparation Co., Ltd. And LtdDIKFILM® was produced by Dikang Biomedical Co., Ltd. METHODS: Sixty rats were allocated into the control, CMCH-CMC membrane and DIKFILM® groups, with 20 animals in each group. In the control group, conventional nerve repair was carried out following the transaction of the sciatic nerve, while in the experimental group, following repair of the nerve, the repair line was covered by CMCH-CMC membrane or DIKFILM® extending 1 cm beyond the distal and proximal ends. MAIN OUTCOME MEASURES: Nerve regeneration and extraneurial adhesion formation were compared between 3 groups at 12 weeks after operation. RESULTS: It was observed that adhesion in the surrounding tissue and neuroma were significantly less in the CMCH-CMC membrane and DIKFILM® group than that in the control group, and more earlier in the functional resume of the limbs. Histological sections obtained from the repair line demonstrated that extraneural and intraneural fibrosis was significantly lower in the CMCH-CMC membrane and DIKFILM® group. The differences between CMCH-CMC membrane and DIKFILM® group had no significant. The nerve conduction velocity and action potential amplitude in each group was increased at 12 weeks after operation than that of 4, and 8 weeks (P < 0.05); the nerve conduction velocity of CMCH-CMC membrane and DIKFILM® group was faster with higher action potential amplitude compared to the control group (P < 0.05). CONCLUSION: The nerve tube made by CMCH-CMC membrane suture following nerve diameter had a favorable effect on nerve regeneration, as well as preventing neuroma formation.