Xueshisanjia San Prevents Liver Fibrosis via PINK1/Parkin Signaling Pathway-mediated Mitophagy
10.13422/j.cnki.syfjx.20260415
- VernacularTitle:薛氏三甲散调控PINK1/Parkin信号通路介导的线粒体自噬抗肝纤维化作用及机制
- Author:
Baojia WANG
1
;
Mulan HU
1
;
Yuanyuan GONG
1
;
Jie MA
2
;
Xiuli ZHENG
1
;
Xiongbin CHEN
1
Author Information
1. School of Basic Medical Sciences， Chengdu University of Traditional Chinese Medicine， Chengdu 611137，China
2. Genetic Diseases Key Laboratory of Sichuan Province， Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital， Chengdu 611137，China
- Publication Type:Journal Article
- Keywords:
liver fibrosis;
Xueshisanjia San;
PTEN-induced putative kinase （PINK1）/Parkin signaling pathway;
mitophagy
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(14):166-175
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the therapeutic effect and mechanism of Xueshisanjia San against liver fibrosis by regulating PTEN-induced putative kinase （PINK1）/Parkin signaling pathway-mediated mitophagy. MethodsForty specific pathogen free （SPF）-grade male C57BL/6 mice were randomized into the control， model， silibinin （100 mg·kg-1）， high-dose （15.16 g·kg-1） Xueshisanjia San， and low-dose （7.58 g·kg-1） Xueshisanjia San groups. The mouse model of liver fibrosis was constructed by intraperitoneal injection of 20% carbon tetrachloride solution. The treatment lasted for 6 weeks. Blood was collected from the abdominal aorta after intraperitoneal anesthesia， and the liver was separated. Liver pathology was examined by hematoxylin-eosin （HE） staining， Masson staining， and Sirius Red staining. Transmission electron microscopy （TEM） was employed to observe the mitochondrial morphology in the liver tissue. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， C-reactive protein （CRP）， total bilirubin （TBil）， transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） in the serum of mice were measured by enzyme-linked immunosorbent assay. Immunohistochemistry， immunofluorescence assay， and Western blot were employed to determine the protein levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and collagen Ⅰ， as well as mitophagy markers microtubule-associated protein 1 light chain 3 （LC3）， p62， Beclin-1， PINK1， Parkin， and translocase of outer mitochondrial membrane 20 （TOM20）. ResultsCompared with the control group， the model group exhibited elevated levels of ALT， AST， CRP， TBil， IL-6， TGF-β1， and TNF-α in the serum （P<0.05）， pathological changes such destroyed structure of hepatic lobules， disarrangement of hepatic cells， and collagen accumulation， swollen， vacuolated， and fragment mitochondria， down-regulated expression of p62 and TOM20， and up-regulated expression of LC3， Beclin-1， PINK1， and Parkin （P<0.05）. Compared with the model group， all the treatment groups exhibited declined levels of ALT， AST， CRP， TBil， IL-6， TGF-β1， and TNF-α in the serum （P<0.05）， alleviated pathological damage of liver tissue and mitochondrial damage， up-regulated expression of p62 and TOM20， and down-regulated expression of α-SMA， COL1A1， LC3， Beclin1， PINK1， and Parkin （P<0.05）. ConclusionXueshisanjia San may prevent excessive mitophagy and improve mitochondrial quality by inhibiting PINK1/Parkin signaling pathway， thereby alleviating liver fibrosis.
