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The effect of electroacupuncture on the SIRT3/FOXO3/SOD2 signaling pathway in the substantia nigra of mice with Parkinson′s disease
Received date: 2025-07-10
Online published: 2025-12-25
Objective Mechanism study of electroacupuncture on improving motor coordination in Parkinson′s disease mice model based on silent mating type information regulation 2 homolog 3/forkhead box protein O3/superoxide dismutase 2（SIRT3/FOXO3/SOD2） pathway. Methods A total of 66 C57BL/6 mice were divided into a control group （Ctrl， n = 15） and a model-establishment group （n = 51） using a random number table. The PD mouse model with impaired coordination was established by intraperitoneal injection of 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. Forty-eight successfully MPTP-induced PD model mice were equally divided into four groups using a random number table： the model group （MPTP， n = 12）， the EA group （EA， n = 12）， the inhibitor group （3-TYP， n = 12）， and the inhibitor + EA group （3-TYP + EA， n = 12）.The Ctrl group was given an equal volume of normal saline. The MPTP group received intraperitoneal injection of MPTP （30 mg/kg） once a day for 7 consecutive days to establish the PD animal model.The EA group was given EA stimulation at the "Fengfu" （GV16） and "Taichong" （LR3） acupoints 2 hours after MPTP injection， once a day for 14 consecutive days.The 3-TYP group was given intraperitoneal injection of 3-TYP （10 mg/kg） 2 hours before MPTP injection. The 3-TYP + EA group received EA stimulation at the "Fengfu" （GV16） and "Taichong" （LR3） acupoints 2 hours after MPTP injection on the basis of the treatment for the 3-TYP group， once a day for 14 consecutive days. In addition， other mice not receiving EA were restrained for 15 minutes. The pole test and hanging test were used to evaluate the motor coordination of mice. Immunohistochemistry was employed to detect the expression of tyrosine hydroxylase （TH） in the midbrain substantia nigra of mice. Western blot was used to measure the protein levels of the SIRT3/FOXO3/SOD2 pathway in the midbrain substantia nigra. Flow cytometry was applied to detect changes in mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） levels in the midbrain substantia nigra of mice. Results Compared with the Ctrl group， the MPTP group showed a significantly prolonged total time in the pole test （P < 0.01）， a significantly decreased score in the hanging test （P < 0.01）， a significantly reduced average optical density of TH in the midbrain substantia nigra （P < 0.01）， a significant down-regulation of SIRT3， FOXO3， and SOD2 contents in the midbrain substantia nigra （P < 0.01）， a significant decrease in MMP （P < 0.01）， and a significant increase in ROS levels （P < 0.01）.Compared with the MPTP group， the EA group exhibited a significantly shortened total time in the pole test （P < 0.01）， a significantly increased score in the hanging test （P < 0.01）， an increased average optical density of TH in the midbrain substantia nigra （P < 0.01）， a significant up-regulation of SIRT3 and SOD2 expressions （P < 0.01）， an increased FOXO3 content （P < 0.05）， a significant increase in MMP （P < 0.01）， and a significant decrease in ROS levels in the midbrain substantia nigra （P < 0.01）.There were no significant differences in all the above indicators between the 3-TYP group and the MPTP group （P > 0.05）. Compared with the EA group， the 3-TYP group had a prolonged total time in the pole test （P < 0.01）， a significantly decreased score in the hanging test （P < 0.01）， a reduced average optical density of TH in the midbrain substantia nigra （P < 0.01）， a significant down-regulation of SIRT3 and SOD2 expressions （P < 0.01）， a decreased FOXO3 content （P < 0.05）， a significant decrease in MMP （P < 0.01）， and a significant increase in ROS levels （P < 0.01）.Compared with the 3-TYP group， the 3-TYP + EA group had increased protein expressions of SIRT3 （P < 0.05）， while there were no significant differences in the other above-mentioned indicators （P > 0.05）. Conclusions EA can activate the SIRT3/FOXO3/SOD2 signaling pathway， inhibit the excessive accumulation of ROS， and alleviate mitochondrial oxidative stress， thereby protecting TH in the midbrain substantia nigra and improving motor coordination in PD model mice. However， EA cannot completely reverse the effect of the SIRT3 inhibitor.
Key words： electroacupuncture; Parkinson′s disease; mitochondria; SIRT3; FOXO3; SOD2
Ling QI , Chuan HE , Yao WANG , Xiaolei ZHANG , Jun. MA . The effect of electroacupuncture on the SIRT3/FOXO3/SOD2 signaling pathway in the substantia nigra of mice with Parkinson′s disease[J]. The Journal of Practical Medicine, 2025 , 41(24) : 3815 -3823 . DOI: 10.3969/j.issn.1006-5725.2025.24.004
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