Chen L E, Liu K, Seaber A V, Katragadda S, Kirk C, Urbaniak J R
Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Neurochem Int. 1998 Oct;33(4):341-51. doi: 10.1016/s0197-0186(98)00037-0.
This in vivo double-blind study evaluated the effect of recombinant human glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the recovery of motor function of rat sciatic nerve following crush injury. Seventy three rats were divided into three groups. Group I (n=5), sham operated; Groups II (n=34) and III (n=34) received a 100 g crush load for 2 h over a 5 mm segment of the sciatic nerve. Group III was treated with 1 mg/kg rhGGF2, via subcutaneous injection one day before nerve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery was assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum longus (EDL) muscle. Recovery of nerve function was evident at day 11 after crush in the rhGGF2-treated animals, whereas the nerves in controls were still paralyzed. The rhGGF2-treated animals showed a significant improvement of the SFI between days 11-21 postoperatively when compared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant difference at 40 to 70 Hz stimulus frequencies on day 4. Correlation analysis showed that tetanic contractile force had a linear correlation with the SFI. Histologic assessment indicated that the rhGGF2-treated animals showed less severe degeneration and earlier robust remyelination of axons than controls. The results suggest that treatment with rhGGF2 is effective in promoting nerve regeneration as seen in measurements of functional recovery and qualitative assessment of nerve morphology. The mechanism of GGF's protective effect may be related to its direct action on Schwann cells, stimulating their mitosis as well as inducing neurotrophic factors essential to neuronal maintenance and repair.
这项体内双盲研究评估了重组人神经胶质生长因子2（rhGGF2，一种雪旺细胞促分裂原）对大鼠坐骨神经挤压伤后运动功能恢复的影响。73只大鼠被分为三组。第一组（n = 5），假手术；第二组（n = 34）和第三组（n = 34）在坐骨神经5毫米节段上接受100克挤压负荷2小时。第三组在神经挤压前一天通过皮下注射给予1毫克/千克rhGGF2，并在随后四天每天注射一次。第二组接受等量的生理盐水作为对照。通过计算坐骨神经功能指数（SFI）和趾长伸肌（EDL）肌肉强直收缩力的恢复率来评估运动功能恢复情况。在rhGGF2治疗的动物中，挤压伤后第11天神经功能恢复明显，而对照组的神经仍处于麻痹状态。与对照组相比，rhGGF2治疗的动物在术后第11 - 21天SFI有显著改善。在rhGGF2治疗组中，等长强直收缩力比对照组更强，在第4天40至70赫兹刺激频率下有显著差异。相关性分析表明，强直收缩力与SFI呈线性相关。组织学评估表明，与对照组相比，rhGGF2治疗的动物轴突的变性较轻，髓鞘再生更早且更旺盛。结果表明，rhGGF2治疗在促进神经再生方面是有效的，这在功能恢复测量和神经形态学定性评估中都有体现。GGF保护作用的机制可能与其对雪旺细胞的直接作用有关，刺激其有丝分裂以及诱导对神经元维持和修复至关重要的神经营养因子。
