关键词: 帕金森病, 6-羟多巴胺, nanog基因, 小胶质细胞, 肿瘤坏死因子α

Abstract: Objective To observe the effects of nanog on the activation of microglial cells and expression of tumor necrosis factor-α (TNF-α) in the substantia nigra (SN) of Parkinson disease (PD) rats induced by 6-Hydroxydopamine (6-OHDA). Methods Sprague-Dawley (SD) rats were randomly divided into control group, 6-OHDA+PBS, 6-OHDA+PNL and 6-OHDA+nanog group. 6-OHDA was injected into the left striatum of brain in experimental model groups, and meanwhile each model group rat received a brain injection of phosphate buffered saline (PBS), lentiviral vector PNL-IRES.EGFP (PNL) or nanog gene vector respectively. On the 14th day after injection, the apomorphine (APO) was injected to induce the rotational behavior, and the APO-induced rotational behavior was observed. The number of tyrosine hydroxylase (TH) positive dopaminergic neurons in the substantia nigra was counted with immunohistochemical staining method, the microglial cell amount and TNF-α expressional level were detected by immunofluorescent staining. Results On the postinjection 14th day, APO induced rotation frequency in 6-OHDA+nanog group was lower than those in 6-OHDA+PNL and 6-OHDA+PBS groups (P<0.05). The numbers of dopaminergic neurons in experimental groups were significantly reduced than control group(P<0.05), but in 6-OHDA+nanog group was significantly higher than those in 6-OHDA+PNL and 6-OHDA+PBS groups (P<0.05). The number of microglial cells and the expression of TNF-α in the left substantia nigra of model rats increased than control group(P<0.05), but those in 6-OHDA+nanog group were less than those in 6-OHDA+PNL and 6-OHDA+PBS groups (P<0.05). Conclusion Nanog gene transfer can protect dopaminergic neurons by inhibiting the microglial cell activation and proceeding inflammatory reaction.

Key words: Parkinson disease, 6-Hydroxydopamine, nanog gene, microglial cell, tumor necrosis factor-α