金属硫蛋白对全脑缺血再灌注后损伤神经的修复作用

The reparation of metallothionein to the injuried neuron after cerebral ischemia and reperfusion in rats

目的:观察金属硫蛋白(Metallothionein,MT)外源性补充对大鼠全脑缺血再灌注(Cerebral ischemia and reperfusion,I/R)损伤的保护作用,并初步探讨其可能机制。方法:建立I/R模型,采用低血压并双侧颈总动脉夹闭的全脑缺血再灌注模型。缺血20 min再灌注1 d后,测行为学指标,石蜡切片HE染色观察海马神经元形态变化,并用免疫组化方法检测海马神经生长因子-β(Nerve growth factor-β,NGF-β)的表达。结果:MT脑室注射给药(1.4、4.2 mg/kg)能剂量依赖性的减轻大鼠行为学症状,增加大鼠海马神经元NGF-β的表达(0.46、1.4、4.2 mg/kg)。同时病理组织学观察还发现,MT(0.46、1.4、4.2 mg/kg)能显著减少I/R大鼠海马区神经元的固缩,增加存活细胞的数量,减轻脑损伤。结论:MT对脑缺血再灌注损伤有神经保护作用,可能机制为促损伤神经元修复。

Objective ：To observe the protect action of exogenous metallothionein on rats＇ cerebral ischemia and reperfusion and explore its possible mechanism. Methods：I/R modle was established. After 20min ischemia and 1 d reperfusion, determined the ethology index and the HE staining was determined to see the morphologic changes of neurons in hippocampus. The expression of NGF-β in hippoeampus was determined by immunohistochemistry. Resluts：Metallothionein cerebral ventricle injection （1.4,4.2 mg/kg）could significantly reduce the ethology symptom by dose dependent, the expression of NGF-β in hippocampus also was increased（0.46,1.4.4.2 mg/kg）.Meanwhile ,the pathological examination showed that the karyopycnosis of neurons in hippocampus with I/R in rats could be decreased by MT uncommonly, which mitigated the injury of brain. Conclusion： MT can protect the brain from I/R injury, its active mechanism may be related to repair impaired neurones.