Effects of electroacupuncture on mitochondrial autophagy and Sirt1/FOXO3/PINK1/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury.
10.13703/j.0255-2930.20231012-k0005
- Author:
Kaiqi SU
1
;
Zhuan LV
1
;
Ming ZHANG
1
;
Lulu CHEN
2
;
Hao LIU
2
;
Jing GAO
1
;
Xiaodong FENG
3
Author Information
1. Rehabilitation Center, First Affiliated Hospital of Henan University of CM, Zhengzhou 450000, China.
2. College of Rehabilitation Medicine, Henan University of CM, Zhengzhou
3. Rehabilitation Center, First Affiliated Hospital of Henan University of CM, Zhengzhou 450000, China; College of Rehabilitation Medicine, Henan University of CM, Zhengzhou
- Publication Type:Journal Article
- Keywords:
Point GV20 (Baihui);
Point GV24 (Shenting);
cerebral ischemia reperfusion injury;
electroacupuncture;
learning-memory impairment;
mitochondrial autophagy
- MeSH:
Animals;
Electroacupuncture;
Male;
Rats, Sprague-Dawley;
Rats;
Forkhead Box Protein O3/genetics*;
Reperfusion Injury/metabolism*;
Ubiquitin-Protein Ligases/genetics*;
Brain Ischemia/complications*;
Mitochondria/genetics*;
Autophagy;
Protein Kinases/genetics*;
Sirtuin 1/genetics*;
Humans;
Memory Disorders/psychology*;
Signal Transduction
- From:
Chinese Acupuncture & Moxibustion
2025;45(2):193-199
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury.
METHODS:A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot.
RESULTS:After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001).
CONCLUSION:EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.