尼古丁对鱼藤酮诱导帕金森病小鼠模型的神经保护作用机制.

BACKGROUND: Studies have found that nicotine can activate the dopamine system, slowing the progression of Parkinson’s disease, but the specific mechanism is still unclear. Research on the neuroprotective mechanism of nicotine in animal models of Parkinson’s disease is lacking. OBJECTIVE: To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson’s disease in mice. METHODS: Twenty-eight C57BL/6 mice were randomly divided into vehicle group, rotenone group, autophagy agonist group and nicotine group, with seven mice in each group. Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice, and the autophagy agonist (rapamycin) or nicotine was given before modeling. The spatial exploration function of the mice was observed by open field test. Western blot and Q-PCR were used to detect the expression of α-synuclein, autophagy related factors Beclin-1 and P62, and apoptosis-related factors Bax, Bcl-2 and Cleaved-caspase3 in the nigra of each group. The deposition of mitochondria, autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy. The survival of neurons was observed by Nissl staining. The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION: The open field test showed that the distance, average speed and time of movement were reduced in the rotenone group compared with the solvent group. Compared with the rotenone group, the exercise distance, average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group (P < 0.05). The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group. Compared with the rotenone group, the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group. Western blot and Q-PCR results showed that compared with the solvent group, the expressions of α-synuclein and P62 in the rotenone group were increased, while Beclin-1 expression was decreased (P < 0.05); compared with the rotenone group, the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group, and the expression of Beclin-1 increased (P < 0.05). Compared with the solvent group, the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group (P < 0.05); compared with the rothenone group, the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups (P < 0.05). To conclude, nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson’s disease mouse models by improving autophagy dysfunction and reducing apoptosis. [ABSTRACT FROM AUTHOR]