不同剂量维生素E对大鼠脑缺血再灌注后GAP-43及突触素P38表达的影响

目的 研究不同剂量维生素E（VitE）对大鼠局灶性脑缺血再灌注后梗死周围区生长相关蛋白-43（GAP-43）及突触素P38表达的影响,从而进一步探讨抗氧化剂在脑缺血损伤中的作用机制及VitE应用剂量.方法 成年健康雌性Wistar大鼠125只,随机分成假手术组、对照组、大剂量VitE组（300 mg/kg）、中剂量VitE组（50 mg/kg）和小剂量VitE组（2.5 mg/kg）.采用线栓法建立大脑中动脉缺血再灌注（MCAO）动物模型.各组分别于术后6 h、1 d、3 d.7 d、14d取脑片.应用免疫组化方法观察脑缺血再灌注后GAP-43和P38的表达.结果 （1）小剂量VitE组GAP-43和P38表达较对照组有所增高,但差异无显著性（P＞0.05）.（2）大、中剂量VitE组间GAP-43和P38表达比较未见明显变化（P＞0.05）.（3）大、中剂量VitE组与对照组比较：GAP-43表达增高,1 d、3 d、7 d、14 d各时间点差异均有显著性（P＜0.05）;P38表达也增高,3 d,7 d、14 d时间点差异具有显著性（P＜0.05）.结论 抗氧化剂VitE可增强中枢神经系统损伤后神经元再生重塑功能.对于VitE最佳剂量的选择,尚有待进一步研究.

Effects of various doses of Vitamin E on expressions of GAP-43 and synapto-physin after cerebral ischemic reperfusion in rats

Objective To study the effect of different doses of Vitamin E onexpressions of growth associated protein-43(GAP-43) and synaptophysin(P38)at damaged side after focal cerebral ischemic reperfusion,and to explore their roles in cerebral ischemia and reperfusion injury in rats and the relationship between doses of Vitamin E and the effects were studied.Methods One hundred and twenty-five adult female rats were divided randomly into sham-operation group,controlled group,high-dose VitE group(300 mg/kg,HVE),middle-dose VitE group(50 mg/kg,MVE)and low-dose VitE group(2.5 mg/kg,LVE).The focal cerebral ischemia/reperfusion models of rats were received right middle cerebral artery occlusion(MCAO).The sections of the brains were obtained and expressions of GAP-43 and P38 with immunochemistry were analyzed at 6 hours and 1,3,7,14 days after reperfusion.Results(1) The expressions of Ref-1,GAP-43 and P38 were slightly increased after low-dose VitE treatment,but there were no difference in above indexes between LVE group and controlled group(P>0.05).(2) The differences were not remarkable in the expression of Ref-1,GAP-43 and P38 between HVE group and MVE group(P>0.05).(3) Compared high-dose and low-dose VitE treatment groups with controlled groups,GAP-43 immunocompetence were elevated and the differences were remarkable at 1,3,7 and 14 days(P<0.05);the expression of P38 were increased and the differences were remarkable at 3,7,14 days(P<0.05).Conclusion This study suggests vitamin E,as an antioxidant,might be accelerate neuronal plasticity and reconstruction in central nervous system after reperfusion injury.But the optimum dosage of vitamin E needs further exploration.