局灶性脑缺血再灌注时胶质细胞源性神经营养因子在大鼠脑组织表达及其意义的实验研究

目的观察胶质细胞源性神经营养因子（glial cell fine-derived neuno-trophic factor，GDNF）在大鼠脑缺血再灌注时的表达特点，及其在脑缺血再灌注中的作用。方法阻断大鼠大脑中动脉（middle cerebral artery，MCA）血流2h，再灌注3—120h制成脑缺血再灌注模型。苏木精－伊红染色评价缺血性脑损伤的组织学特点，免疫组织化学（immunohistochemistry，IHC）染色观察GDNF、iNOS表达特点。结果再灌注12h组开始出现神经元不可逆变性，24h梗死形成。正常组和假手术组未检测到GDNF的表达。再灌注3—120h，在整个再灌注过程中GDNF阳性的细胞在3h达到高峰，后逐渐下降，各组与再灌注3h组比较P〈0．01。结论脑缺血后再灌注，变性、死亡的神经元不表达GDNF，缺血周边区和非缺血区神经元GDNF表达明显增强，提示GDNF有促进神经元存活作用。缺血再灌注时活化的小胶质细胞或巨噬细胞可能表达GDNF。为临床早期使用GDNF减少脑损害，提供了一定的参考价值。

A study on expression and significance of GDNF in cerebral tissue of ratssubjected to cerebral ischemia-reperfusion

Objective To observe the expression of glial cell line-derived neuro-trophic factor（GDNF） in cerebral tissue of rats subjected to cerebral ischemia-reperfusion, and its role in rats following cerebral ischemia-reperfusion. Methods The model of focal cerebral ischemia was made by occluding middle cerebral artery （MAC） for 2h and reperfusion for 3 - 120h, HE staining was used to investigate the histological features of ischemic cerebral damage,the immunohistochemical method was used to observe the expression of GDNF in brain tissue in rats. Results The neurons presented irreversible degeneration at 12h of reperusion. At 24h, the ischemic atea in the preopfic area,striautm and cortex devaioped into infarct form. GDNF Positive cells were not detected in normal and sham-operated rats.During the course of repeffusion, The number of GDNF positive cells peaked at 3h of reperfusion, then gradually decreased. Quantitation analysis reveals that the number of GDNF immunoreactive cells in the ipsilateral-ischemic area significantly{ P 〈 0.01 ） decreased 12,24,48,72and 120h after MAC occlusion compared with that of 3h after MAC occlusion. Conclusion During cerebral ischemia-reperfusion,the degenerative and died nenron do not express GDNF and neurons in peri-ischemic area and no-ischemic area showed GDNF immunoreactivity. These results suggest that GDNF has a potential to protect neurons from in jury. Activated microglias or macrophages can express GDNF during ischemia injury The study provides a certain referance value to use GDNF in early phase of cerebral ischemic to decrease cerebral in jmy.