米诺环素对大鼠视神经损伤后视网膜胶质源性神经营养因子表达的影响

Effect of minocycline on the expression of glial cell-derived neurotrophic factor in retina of rats after optic nerveinjury

【摘要】目的通过对大鼠视神经损伤后视网膜胶质细胞源性神经营养因子（GDNF）表达的研究，探讨米诺环素（MC）对视神经损伤后视网膜神经节细胞（RGCs）的保护作用及其机制。方法53只SD大鼠，随机分为正常对照组3只，实验一生理盐水对照组25只，实验一米诺环素治疗组25只。两实验组每只动物左眼行视神经损伤，之后分别向腹腔注入等量生理盐水或米诺环素，于损伤后1d、3d,7d、14d、28d取材，苏木精一伊红（HE）染色观察RGCs形态及数目变化，免疫组化半定量检测视网膜组织活化GDNF的平均光密度值。结果HE染色示各时间点治疗组较对照组大鼠视网膜神经节细胞层胞核排列相对密集整齐，RGCs空泡化程度轻，除1d时间点外，各治疗组RGCs细胞数量均高于对照组，差异均有统计学意义（P〈0．05）。免疫组织化学结果示除1d时间点外，各时间点治疗组较对照胶质细胞源性神经营养因子（GDNF）的表达强，结果有统计学意义（P〈0．05）。结论米诺环素能增强视神经损伤后早期视网膜GDNF的表达，对损伤后RGCs有较强的保护作用。

Objective To explore the neuroprotective mechanism of minocycline on retinal ganglion cells （RGC） by investigating the effect of minocycline on the expression of glial cell-derived neurotrophic factor （GDNF） in retina of rats after optic nerve injury. Methods Fifty-three SD rats were randomly divid- ed into three groups： control group （3 rats）, saline group （25 rats） and experimental group （25 rats）. The left eyes in the saline and experimental group were made into the model of optic nerve injury. 45 mg/kg mi- nocycline or the same dose of normal saline was injected intraperitoneally in the rats of experimental group or saline group, respectively. The rats were euthanized at 1 d, 3 d, 7 d, 14 d and 28 d postoperatively and the retina was collected. The morphological changes and the counting results of RGC were shown by hematoxylin- eosin staining. The concentration of active GDNF in retina was tested by semi-quantitative immunohistochem- istry. Results The RGCs in the experimental group were more tidy with less degree of cytoplasmic vacuole formation than that in the saline group. The average number of RGC was higher in the experimental group than the saline group at all time points except 1 d. The differences were statistically significant （ P 〈 0.05 ）. The concentrations of GDNF were higher in the experimental group than the saline group at all time points （ P 〈 0.05）. Conclusion Minocycline protects RGC through enhancing the expression of GDNF in the early stage after injury.