MANF减轻帕金森病大鼠模型的神经损伤

MANF alleviates the neural lesion in rat model of Parkinson's disease

目的观察中脑星形胶质细胞源性神经营养因子(MANF)对6-OHDA引起的多巴胺能神经元损伤的影响。方法表达纯化人重组MANF蛋白;将6-OHDA立体定位注射至大鼠纹状体区,制备大鼠帕金森模型;将3个剂量(5、10、20μg)纯化的MANF注射至模型大鼠纹状体区,腹腔注射司来吉兰作为阳性对照,纹状体直接注射PBS作为阴性对照;计数大鼠给药前后由阿扑吗啡诱导的由损伤侧向健侧不对称的旋转次数;免疫组化方法检测各大鼠黑质、纹状体部位酪氨酸羟化酶(TH)阳性神经元和神经纤维。结果 10μg MANF组大鼠的旋转行为较PBS组明显减少,效果与司来吉兰组相近。MANF注射后对黑质部位TH阳性神经元数量和纹状体部位TH阳性神经纤维数量均有不同程度的明显恢复。结论 MANF能减轻6-OHDA引起的帕金森模型大鼠的神经损伤。

Objective To observe whether MANF （mesencephalic astrocyte-derived neurotrophic factor） is effec- tive in restoration of 6-OHDA lesioned dopaminergic neurons. Methods Human recombinant MANF was expressed and purified; The model of Parkinson＇ s disease was prepared by injecting 6-OHDA into the striatums of the rats with a stereotaxie frame ; The purified protein of MANF, with three doses of 5, 10 and 20 μg, or PBS （ as a negative control） was injected into the same site of striatums of rats; Selegiline was intraperitoneally injected as a posi- tive control ; The behavioral performance was tested by counting the times of apomorphine-induced rotational activity from lesion side to the intact side; The numbers of tyrosine hydroxylase （TH） positive neurons and fibers in sub- stantial nigra （SN） and striatum （STR） in each group of rats were observed by immunohistochemistry. Results 10 p.g of MANF was effective to reduced the behavioral performance of the PD rats compared with^PBS group. Sele- giline showed the similar effect on PD rats. Meanwhile, compared with PBS treatment, the numbers of the TH posi- tive neurons in the parts of SN and the neuronal fibers in the parts of STR was significantly increased in the PD rats which treated with MANF and selegiline. Conclusion MANF restores the impairment of dopaminergic neurons in- duced by 6-OHDA.