Journal of Jilin University(Medicine Edition) ›› 2022, Vol. 48 ›› Issue (3): 638-647.doi: 10.13481/j.1671-587X.20220312

• Research in basic medicine • Previous Articles    

Protective effect of lidocaine on PC12 cells in Parkinson’s disease model and its mechanism

Xiaochen HUANG1,Hao LI2,Baohua WANG1(),Kai LI2,3()   

  1. 1.Department of Anesthesiology,Affiliated Hospital,Changchun University of Traditional Chinese Medicine,Changchun 130117,China
    2.Department of Labor Health and Environmental Health,School of Public Health,Jilin University,Changchun 130021,China
    3.Department of Anesthesiololgy,China-Japan Union Hospital,Jilin University,Changchun 130033,China
  • Received:2021-09-22 Online:2022-05-28 Published:2022-06-21
  • Contact: Baohua WANG,Kai LI E-mail:wbhzyxx@163.com;likai@jlu.edu.cn

Abstract: Objective

To investigate the protective effect of lidocaine on the PC12 cells in Parkinson’s disease(PD) model induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), and to elucidate its possible molecular mechanism.

Methods

CCK-8 method was used to determine the optimal concentration and time of MPTP with different concentrations (0.2, 0.4, 0.8, 1.6, and 3.2 mmol·L-1). CCK-8 method was used to determine the optimal concentration and time of lidocaine with different concentrations (0.001, 0.010, 0.100, 0.200, 0.400, 0.600, 0.800, and 1.000 g·L-1), and Western blotting method was used to further determine the optimal concentration of lidocaine. The PC12 cells were divided into control group, MPTP group(0.8 mmol·L-1 MPTP for 24 h), MPTP+ lidocaine group(given 0.8 mmol·L-1 MPTP for 24 h, followed by 0.6 g·L-1 lidocaine for 6 h), MPTP+ lidocaine +DKK1 group(given 0.8 mmol·L-1 MPTP for 24 h, followed by 0.6 g·L-1 lidocaine and 100 μg·L-1 DKK1 for 6 h), and MPTP+DKK1 group(given 0.8 mmol·L-1 MPTP for 24 h, followed by 100 μg·mL-1 DKK1 for 6 h). Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in the PC12 cells in various groups. The expression levels of interleukin-1β(IL-1β), interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α) in supernatant of the PC12 cells in various groups were detected by ELISA assay;real-time fluorescence quantitative PCR (RT-qPCR) method was used to detect the expression levels of Wnt ligand protein 1 (Wnt1),β-catenin,and glycogen synthase kinase-3β(GSK-3β) mRNA in the PC12 cells in various groups.The expression levels of Wnt1, β-catenin, GSK-3β, phosphorylated GSK-3β (p-GSK-3β), and cysteine aspartate protease 3 (caspase 3) proteins in the PC12 cells in various groups were detected by Western blotting method.

Results

Compared with control group, the levels of ROS, IL-1β, IL-6 and TNF-α,and the expression levels of GSK-3β mRNA, and the expression levels of GSK-3β, p-GSK-3β, caspase 3 proteins in the PC12 cells in MPTP group were significantly increased(P<0.05), and the expression levels of Wnt1, β-catenin mRNA and proteins were significantly decreased(P<0.05). Compared with MPTP group, the levels of ROS, IL-1β, IL-6, and TNF-α and the expression levels of GSK-3β mRNA, and the expression levels of GSK-3β, p-GSK-3β, and caspase 3 proteins in the PC12 cells in MPTP+lidocaine group were significantly decreased(P<0.05), however, the expression levels of Wnt1 and β-catenin mRNA and proteins were significantly increased(P<0.05).

Conclusion

Lidocaine can significantly reduce the production of ROS and inhibit the release of pro-inflammatory cytokines in the PC 12 cells, and also significantly down-regulate the expression of apoptotic protein caspase 3, thus playing a protective role in the MPTP-induced PD model PC12 cells; its mechanism may be related to the Wnt /β-catenin signaling pathway.

Key words: Parkinson’s disease, Lidocaine, Oxidative stress, Wnt ligand protein 1, PC12 cells

CLC Number: 

  • R614.1