Tham S, Dowsing B, Finkelstein D, Donato R, Cheema S S, Bartlett P F, Morrison W A
Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Melbourne, Australia.
J Neurosci Res. 1997 Jan 15;47(2):208-15.
The cytokine leukemia inhibitory factor (LIF) favors the survival and growth of axons in vitro and in vivo. Fibronectin has been shown to enhance nerve regeneration when added in combination with various growth factors including LIF. The goal of this study was to evaluate the effect of LIF plus fibronectin on the regeneration of transected nerve and functional recovery of reinnervated skeletal muscle, in one experimental model of peripheral nerve repair, at two recovery times. The rat sciatic nerve was cut at mid-thigh level and a silicone cuff containing either saline (control), LIF, or LIF plus fibronectin (L+F) was used to bridge the proximal and distal nerve stumps leaving a 1 cm gap between them. Rats were then explored at 6 or 12 weeks following the initial surgery. Regenerating nerves were assessed by measuring the diameter of myelinated axons, conduction velocity, and number of myelinated fibers. Muscle reinnervation was assessed by measuring muscle mass, force of contraction, and histologically for changes in muscle fiber type (type I and type II). In this report we demonstrate that at 6 weeks there were significant increases in 1) nerve conduction velocity, 2) myelinated axon diameter, and 3) number of myelinated axons over that of control (saline-treated) animals. Both LIF groups demonstrated a shift in type II muscle fiber area compared to saline-treated controls, with the L+F group having a significant increase in muscle mass. At 12 weeks there was an improved recovery over and above that demonstrated at 6 weeks. Muscle mass was 65% and 42% greater than control for LIF and L+F, respectively. Force of contraction, conduction velocity, myelinated fiber number, and diameter were also significantly greater for both LIF- and L+F-treated rats than saline-treated rats. These results demonstrate that LIF significantly improves the regeneration of damaged peripheral nerves and the preservation of muscle viability, resulting in greatly enhanced recovery of skeletal muscle function.
细胞因子白血病抑制因子（LIF）在体外和体内均有利于轴突的存活和生长。研究表明，纤连蛋白与包括LIF在内的多种生长因子联合使用时，可增强神经再生。本研究的目的是在一个外周神经修复的实验模型中，于两个恢复时间点评估LIF加纤连蛋白对横断神经再生及再支配骨骼肌功能恢复的影响。大鼠坐骨神经在大腿中部水平切断，使用含有生理盐水（对照组）、LIF或LIF加纤连蛋白（L+F）的硅胶套管桥接近端和远端神经残端，二者之间留1 cm间隙。然后在初次手术后6周或12周对大鼠进行检查。通过测量有髓轴突直径、传导速度和有髓纤维数量来评估再生神经。通过测量肌肉质量、收缩力，并进行组织学检查以观察肌纤维类型（I型和II型）的变化来评估肌肉再支配情况。在本报告中，我们证明，在6周时，与对照组（生理盐水处理组）动物相比，1）神经传导速度、2）有髓轴突直径和3）有髓轴突数量均显著增加。与生理盐水处理的对照组相比，两个LIF组的II型肌纤维面积均发生了变化，L+F组的肌肉质量显著增加。在12周时，恢复情况比6周时有所改善。LIF组和L+F组的肌肉质量分别比对照组大65%和42%。LIF和L+F处理的大鼠的收缩力、传导速度、有髓纤维数量和直径也均显著高于生理盐水处理的大鼠。这些结果表明，LIF可显著改善受损外周神经的再生及肌肉活力的维持，从而极大地增强骨骼肌功能的恢复。
