Chinese Journal of Pharmacovigilance ›› 2021, Vol. 18 ›› Issue (4): 306-311.
DOI: 10.19803/j.1672-8629.2021.04.02

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Study on MPTP-induced Parkinson's Disease-like Pathological Changes in Mice Liver

HAN Qiwen, CHEN Ying, CHEN Naihong, YUAN Yuhe*   

  1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • Received:2020-11-04 Online:2021-04-15 Published:2021-04-23

Abstract: Objective To investigate the physiological function and pathological changes of the liver in a mouse model of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced Parkinson's disease (PD). Methods Male C57BL/6 mice were randomly divided into the control group and model group. The model group received subcutaneous injection of MPTP combined with an intraperitoneal injection of probenecid (MPTP/p) every 4 days with MPTP/p for 10 times, while the control group was injected with physiological saline in the same way. The pathological changes of the mouse liver were assessed by Hematoxylineosin staining (HE), while the changes of different forms of α-synuclein (α-syn) in the liver, and those of expressions of 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-Nonenal (4-HNE) were measured using an immunohistochemical method. The level of ROS in the liver was detected by dihydroethidium (DHE) staining with a fluorescent probe of reactive oxygen species (ROS). Western blot and immunofluorescence were used to detect the distribution of nuclear factor erythroid-2 related factor 2 (Nrf2) in the nucleus and cytoplasm of liver tissue. Results In the PD mouse model induced by MPTP/p, liver tissue showed obvious inflammatory infiltration. The levels of the nitrated form of α-syn (n-syn) and oligomeric form of α-syn (5G4) protein increased. DNA damage and oxidative stress occurred in liver tissue. The expression of total Nrf2 protein in liver cells was up-regulated, but Nrf2 in the cytoplasm was reduced significantly. Conclusion PD pathogenic factors can induce significant changes in the pathological structure and physiological functions of the liver in model animals. The above changes are closely related to oxidative stress, and α-syn can be used as an indicator molecule for body disease.

Key words: MPTP, Parkinson's disease, liver, α-synuclein, oxidative stress

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