肝细胞生长因子对喉返神经损伤后再生的作用

Experimental Study of Effect of Hepatocyte Growth Factor on Recurrent Laryngeal Nerve Regeneration in Dogs

目的探讨肝细胞生长因子(hepatocyte growth factor,HGF)局部应用对受损喉返神经再生的作用。方法 20只健康杂种犬分成HGF组及对照组,每组10只。每只犬切断左侧喉返神经后,用聚乳酸聚羟基乙酸共聚物[Poly(DL lactide co glycolide),PLGA]管桥接左侧喉返神经断端,HGF组于PLGA管内及局部应用HGF,对照组同法应用等量生理盐水。于术后2、3、4个月分别行电子喉镜、喉返神经电生理检查,最后一次检查完后处死动物,取神经干作神经组织学和超微结构观察。结果术后2个月,两组动物术侧声带未恢复运动;术后3个月,HGF组有4只犬的左侧声带观察到内收、外展运动,而对照组均未恢复运动;术后4个月,HGF组存活的8只犬中7只术侧声带恢复运动,对照组7只存活犬中5只术侧声带恢复运动,但运动幅度均明显小于HGF组。术后各时间点HGF组与对照组喉返神经电生理检查结果相比较,HGF组自发肌电图、诱发电位幅度明显增大,潜伏期明显缩短,差异均有统计学意义(P<0.05)。HGF组有髓再生神经纤维数、神经纤维的直径及髓鞘的厚度均明显大于对照组,差异均有统计学意义(P<0.05)。电镜观察示HGF组的再生神经纤维超微结构形态接近正常,而对照组形态与正常差异较大,可见较多的无髓神经纤维。结论喉返神经损伤后应用外源性HGF对其再生有明显的促进作用。

Objective To elucidate the role of HGF in the regeneration of recurrent laryngeal nerve （RLN） after injury. Methods 20 healthy dogs were divided into two groups, the HGF group and the control group. The left RLN were transected in all 20 animals,and two stumps of the left RLN were connected by a graft called poly （lactideco-glycolide） （PLGA） tube. HGF was injected into the PLGA tubes in the left RLN in animals of the HGF group, the same amount of saline were injected into the PLGA tubes in animals of the control group. All animals underwent laryngoscope and electrophysiological examination in 2, 3, 4 month postoperatively. Animals were sacrificed after final examination, neurohistologie and ultrastucture examination were performed on nerve trunk. Results No vocal cord motion was observed in all animals in both groups 2 months postoperatively. Physiological adducto- ry and abductory motion was observed in 4 animals in HGF groups, but none in control group 3 months postoperatively. Vocal cord motion was observed in all 8 surviving animals in HGF group. It was only observed in 5 animals of all surviving 7 animals in the control group 4 months postoperatively. The amplitude of vocal cord motion was much less than that of HGF group. Amplitude of spontaneous EMG and evoked potential in HGF group were significantly increased and latencies in HGF group were significantly shorter than those in control group in corresponding time points, with statisticaly difference （P〈0.95）. The average number and diameter of myelinated axons in HGF group were significantly greater than those in control group （P〈0.05）. Electron microscopy showed that ultrastructural morphology of regenerated nerve fibers in HGF group was close to normal, while that in control group were morphologically diverse. Conclusion The application of exogenous HGF has a definite role in promoting regeneration after recurrent laryngeal nerve injury.