神经元营养活性肽对帕金森病大鼠小胶质细胞保护作用及机制研究

Protection of neuron nutrition active peptide on microglia in Parkinson′s disease rats and its mechanism

目的观察从东亚钳蝎中提取的神经元营养活性肽(NNAP)对帕金森病(PD)大鼠的保护作用及其对小胶质细胞的影响。方法采用6-羟多巴胺(6-OHDA)制备PD大鼠模型,通过行为学检测和中脑黑质致密部的酪氨酸羟化酶(TH)以及OX-42的免疫组织化学染色,同时设立实验给药组,观察NNAP对PD大鼠的旋转行为以及黑质DA能神经元和小胶质细胞的影响。结果 经ip NNAP[蛋白浓度为0.05 mg/(kg.d)]处理7 d后的PD大鼠旋转次数较模型组明显减少(P<0.01)。在6-OHDA大鼠损毁侧,实验给药组与模型组相比,在黑质处20 000μm2测量面积内,DA能神经元的免疫反应阳性神经元数目和吸光度与模型组比较明显增高(P<0.01);小胶质细胞的数目和吸光度与模型组比较明显降低(P<0.01)。结论 NNAP对PD大鼠具有保护作用,抑制小胶质细胞免疫反应活性可能参与其机制。

Objective To observe the protection of neuron nutrition active peptide（NNAP） on the Parkinson′s disease（PD） rats and its effect on the microglias.Methods 6-Hydroxydopamine（6-OHDA） was used to prepare the PD rat model.Further,the effects of NNAP on the rotation behavior and the immunoreactivity of substantial nigra dopaminergic（DA） neurons and microglia cells were observed by behavior test and immunocytochemistry.Results The results show that PD rats treated with NNAP [0.05 mg/（kg·d）,ip] for 7 d behaved the decreased rotation times compared to PD group obviously（P〈0.01）.Furthermore,in the lesion side of 6-OHDA rat,compared with the model group,the therapeutic rats revealed the obvious increased number and the optical density of DA neurons in 20 000 μm2 measure area（P〈0.01）;The obvious decreased number and the optical density of the microglia cells compared to PD group in the midbrain（P〈0.01）.Conclusion The results suggest that NNAP could inhibit the immunoreactivity of microglia cells,which may involve in the protection function in PD rats.