神经生长因子滴眼液对兔眼LASIK术后角膜神经修复的影响

Effect of nerve growth factor eye drops on corneal nerve regeneration in rabbits after LASIK

目的探讨神经生长因子（NGF）对兔眼准分子激光原位角膜磨镶术（LASIK）后角膜神经损伤再生修复的影响。方法实验研究。将15只（30眼）薄瓣LASIK术后新西兰大白兔随机分为NGF组（NGF治疗）、阳性对照组（人工泪液玻璃酸钠滴眼液治疗）与阴性对照组（0．9％氯化钠溶液滴眼），每组各5只（10眼）。利用共聚焦显微镜分别测量术前，术后1周、1个月、3个月中央角膜上皮下神经密度（SND）、上皮下神经数量及浅基质神经密度、浅基质神经数量，并进行比较。采用重复测量方差分析比较不同时间点及3组之间各神经参数的差异。结果术前阴性对照组、阳性对照组、NGF治疗组SND分别为（10801±3331）μm／mm2、（11619±3932）μm／mm2、（12299±2622）μm／mm2，上皮下神经纤维数量分别为12．2±3．4、11．6±9．7、13．1±2．7，浅基质神经密度分别为（7258±1242）μm／mm2、（8148±2462）μm／mm2、（8984±1526）μm／mm2，浅基质神经数量分别为8．5±1．4、8．9±2．6、10．1±2．1。与术前相比，3组所有的神经参数在术后1周均明显减少（P〈0．01）。与术后1周相比，NGF治疗组SND、浅基质神经密度在术后1个月均上升。而阴性对照组和阳性对照组的SND、浅基质神经密度在术后3个月才开始上升，差异有统计学意义（P〈0．01）；3组上皮下神经数量在术后3个月开始上升（P〈0．05）；NGF组和阳性对照组的浅基质神经数量在术后1个月上升（NGF组P〈0．01，阳性对照组P〈0．05），并且NOF组的浅基质神经数量在术后1个月恢复到术前水平。结论NGF滴眼液对LASIK术后角膜神经的损伤再修复有明显促进作用。

Objective To investigate the effect of nerve growth factor （NGF） eye drops on central corneal nerve regeneration in rabbits after laser in situ keratomileusis （LASIK）. Methods This was a experimental study. Fifteen New Zealand white rabbits were randomly assigned to one of three groups： NGF-treatment group, artificial tears hycosan-treatment group （positive control group）, and normal saline-treatment group （negative control group） with five rabbits in each group, one drop every time and three times per day. The nerve density and the number of central corneal sub-basal and stromal cells were measured by confocal microscopy and were compared before surgery and at 1 week, 1 month, and 3 months after surgery. Analysis of variance was used for comparing the differences at different time points and among the three groups. Results The respective preoperative sub-basal nerve densities （SNDs） in the negative control group, positive control group, and NGF treatment group were 10 801±3 331 μm/mm2, 11 619±3 932 μm/mm2, and 12 299±2 622 μm/mm2. The number of corneal sub-basal nerve fibers were 12.2±3.4, 11.6±2.7, and 13.1±2.7 in the respective groups. In the preoperative corneas, the corneal stromal nerve densities were 7 258±1 242 μm/mm2, 8 148±2 462 μm/mm2, 8 984±1 526 μm/mm2, and the number of corneal stromal nerve fibers were 8.5±1.4, 8.9±2.6, 10.1±2.1 in the respective groups. Compared with preoperative values, nerve parameters in all groups increased at 1 week postoperatively （P〈0.01）. Compared with I week postoperative, SNDs and corneal stromal nerve densities in the NGF group increased at 1 month, while the control groups increased at 3 months （P〈0.01）. The number of sub-basal corneal nerve fibers in all three groups increased at 3 months （P〈0.05）. The number of corneal stromal nerve fibers increased at 1 month compared with 1 week postoperative in the NGF group and the positive control group （P〈0.05）. However there were no significant changes in the number of corneal stromal nerve fibers between pre- and postoperative 1 and 3 months measurements. Conclusion NGF eye drops promote corneal nerve repair at different periods following LASIK in rabbit eyes.