脑缺血再灌注恢复期大鼠梗死周围组织GFAP、NSE、SYN、Nogo—A表达与神经功能转归的相关性

Correlation between the GFAP, NSE, SYN and Nogo-A expression and neurological outcome in tissue surrounding the infarct during the recovery after cerebral ischenia-reperfusion injury in rats

目的探讨脑缺血再灌注恢复期大鼠梗死周围组织胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）、神经元特异性烯醇化酶（neuron—specific enolase，NSE）、突触素（synaptophysin，SYN）、神经突生长抑制因子-A（neurite outgrowth inhibitor—A，Nogo—A）表达与神经功能转归的相关性。方法线栓法制作大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）2h再灌注模型，模型制作后28、35、42和49d改良神经功能缺损评分（modified neurological severity score，mNSS），并采用免疫组化方法检测脑梗死周围组织GFAP、NSE、SYN、Nogo—A表达。结果大鼠脑缺血再灌注后随着时间推移，mNSS评分逐渐下降，除第35天（5．11±0．737）与第42天（4．54±0．519）、第42天与第49天（4．29±0．488）无显著差异外，其余各时间点均有显著差异（P均〈0．05）。GFAP阳性细胞数量从第28天至第49天逐渐减少，其中第42天（51．00±13．59）和第49天（44．38±11．94）显著少于第28天（69．00±15．10）（P〈0．05）。NSE表达的累积光密度（integrated optical density，IOD）逐渐增高，第28天（6218．57±1864．25）与第42（9414．00±2491．12）和第49天（12522．50±3106．99），第35天（7343．40±1533．35）与第49天差异显著（P均〈0．05），其余各时间点无显著差异。SYN表达IOD逐渐增高，第49天（66503．00±12834．61）显著高于第28天（43905．14±13208．59）（P〈0．05）。Nogo-A阳性细胞数量逐渐减少，第49天（42．13±14．45）显著少于第28天（59．57±15．25）（P〈0．05）。GFAP表达与mNSS评分呈正相关（r=0．993，P=0．007），NSE（r=～0．954，P=0．044）、SYN（r=-0．992，P=0．008）表达与mNSS评分呈负相关。结论大鼠脑缺血再灌注后恢复期神经功能转归与GFAP表达下调、NSE和SYN表达上调相关。

Objective To investigate the correlation between the gtial fibrillary acidic protein （GFAP）, neuron-specific enolase （NSE）, synaptophysin （SYN）, neurite outgrowth inhibitor-A （Nogo-A） expression and neurological outcome in tissue surrounding the infarct during the recovery after cerebral ischemia-reperfusion injury in rats. Methods A 2-hour middle cerebral artery occlusion （MCAO） and reperfusion model in rats was induced by the intraluminal suture method. The modified neurological severity score （mNSS） was performed at day 28, 35, 42, and 49. Immunohistochemistry was used to detect the expressions of GFAP, NSE, SYN, and Nogo-A in tissue surrounding the infarct. Results The mNSS score decreased gradually over time after cerebral ischemia-repetfusion injury in rats. Except day 35 （5. 11± 0. 737）vs. day 42 （4. 54 ±0. 519）, and day 42 vs. day 49 （4. 29 ±0. 488）, there were significant differences at all other time points （all P 〈0. 05）. The numbers of GFAP positive cells decreased gradually form day 28 to day 49, in which, the numbers of GFAP positive cells at day 42 （51.00 ± 13.59） vs. day 49 （44. 38 ± 11.94） were significantly less than those at day 28 （69. 00 ± 15.10） （P 〈 0. 05）. There were no significant differences in the numbers of NSE positive cells at all time points, but their integrated optical density （IOD） increased gradually. There were significant differences between day 28 （6 218.57±1 864. 25） and day 42 （9 414. 00 ± 2 491. 12） or day 49 （12 522.50 ± 3 106. 99）, and between day 35 （7 343.40 ±1 533.35） and day 49 （all P 〈 0. 05）. There were no significant differences at all other time points. The SYN express （IOD） increased gradually, and it was significantly lower at day 49 （66 503.00 ± 12 834. 61） than that at day 28 （43905. 14± 13208.59） （P〈 0.05）. The numbers of Nogo-A positive ceils decreased gradually, and they were significantly less at day 49 （42. 13 ± 14. 45） than those at day 28 （59. 57 ± 15.25） （P 〈0. 05）. The GFAP expression was positively correlated with the mNSSscores （r=0.993, P=0.007）. The NSE （r= -0.954, P=0.044） and SYN （r= -0. 992, P =0. 008） expression was negatively correlated with the mNSS scores. Conclusion The neurological outcome was associated with the downregulation of GFAP expression and the upregulation of NSE and SYN expression during the recovery after cerebral ischemia-reperfusion injury in rats.