Mechanism of Jiawei Guizhi Fuling Decoction in Alleviating Sciatic Nerve Injury in PDPN Rats by Regulating Mitophagy Through PINK1/Parkin Signaling Pathway
10.13422/j.cnki.syfjx.20241302
- VernacularTitle:加味桂枝茯苓汤通过PINK1/Parkin信号通路调控线粒体自噬途径减轻PDPN大鼠坐骨神经损伤的作用机制
- Author:
Aihua LIU
1
;
Jinhong LENG
2
;
Ziying LIU
1
;
Xinyu SUN
1
;
Xinyuan SHEN
1
;
Qing KANG
1
;
Zhiyi LI
1
;
Yongming LIU
1
Author Information
1. Liaoning University of Traditional Chinese Medicine（TCM），Shenyang 110847，China
2. Affiliated Hospital of Liaoning University of TCM，Shenyang 110032，China
- Publication Type:Journal Article
- Keywords:
painful diabetic peripheral neuropathy;
Jiawei Guizhi Fuling decoction;
mitophagy;
PTEN-induced putative kinase 1/Parkin signaling pathway;
sciatic nerve injury
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(21):42-51
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the mechanism of Jiawei Guizhi Fuling decoction （JGFD） in alleviating sciatic nerve injury in painful diabetic peripheral neuropathy （PDPN） rats by regulating mitophagy through the PTEN-induced putative kinase 1 （PINK1）/Parkin signaling pathway. MethodThe PDPN model was established by intraperitoneal injection of streptozotocin （STZ）. After modeling， the rats were randomly divided into JGFD high， medium， and low dose groups （JGFD-H， JGFD-M， JGFD-L； 39.6， 19.8， 9.9 g·kg-1·d-1， respectively）， a positive drug group （lipoic acid capsules， LA； 50 mg·kg-1·d-1）， and a model group （PDPN）. A blank control group （CON） was established. Drug intervention was administered continuously for 8 weeks after modeling. Measurements included body weight and fasting blood glucose of PDPN rats at weeks 0， 2， 4， and 8， mechanical pain threshold and thermal pain threshold at weeks 0 and 8， and motor nerve conduction velocity at week 8. Hematoxylin-eosin （HE） staining was used to observe the morphology of sciatic nerve tissue. The ultrastructure of mitochondria and autophagosomes was observed by transmission electron microscopy. Western blot was performed to detect the protein expression levels of PINK1， Parkin， p62， Beclin-1， and LC3 in sciatic nerve tissue. Additionally， real-time quantitative PCR （Real-time PCR） was performed to detect the mRNA expression levels of PINK1， Parkin， p62， Beclin-1， and LC3 in sciatic nerve tissue. ResultCompared with the CON group， the PDPN group showed a significant decrease in body weight at all time points， a significant increase in fasting blood glucose， significantly shortened mechanical pain and thermal pain thresholds， and significantly reduced motor nerve conduction velocity. The protein and mRNA expression of PINK1， Parkin， Beclin-1， and microtubule-associated protein light chain 3（LC3） in sciatic nerve tissue was significantly reduced， while p62 protein and mRNA expression was significantly increased （P<0.01）. Pathological changes included edema of sciatic nerve fibers， segmental demyelination， loose and disordered arrangement of the myelin sheath layers， significant swelling of mitochondria， reduced electron density， disappearance of cristae， and absence of typical autophagosome and autolysosome structures. Compared with the PDPN group， each JGFD dose group showed a significant increase in body weight and a significant reduction in fasting blood glucose （P<0.05， P<0.01）. The mechanical pain threshold and thermal pain threshold were significantly prolonged， and motor nerve conduction velocity was significantly increased across all JGFD and LA groups. The expression levels of PINK1， Parkin， Beclin-1， and LC3 proteins and mRNA in sciatic nerve tissue were significantly increased， while p62 protein and mRNA expression levels were significantly decreased （P<0.05， P<0.01）. Pathological damage to the sciatic nerve was alleviated to varying degrees， with a relatively intact myelin sheath morphology and intact or slightly edematous outer mitochondrial membrane. Autophagolysosome structures were observed in the JGFD-M and JGFD-H groups. Compared with the LA group， the JGFD-H group showed a significant increase in body weight， a significant reduction in fasting blood glucose， a significant increase in motor nerve conduction velocity， a significant increase in PINK1 protein expression and PINK1， Parkin， and Beclin-1 mRNA expression in sciatic nerve tissue， and a significant decrease in p62 mRNA expression （P<0.05， P<0.01）. ConclusionJGFD may alleviate sciatic nerve injury in PDPN rats by activating mitophagy through the regulation of the PINK1/Parkin signaling pathway.
