基于PINK1/Parkin线粒体自噬通路探讨疏肝温胆汤抗动脉粥样硬化的分子机制OA

Objective To investigate the interventional effect and molecular mechanism of Shugan Wendan Decoction(疏肝温胆汤,SGWDD)on atherosclerosis(AS)through the PINK1/Parkin-mediated mitophagy pathway.Methods Forty ApoE-/-mice were randomly divided into four groups(n=10 per group):normal control,model,SGWDD,and atorvastatin(positive control)groups.After 12 weeks of treatment,body weight,serum lipid profiles(total cholesterol/TC,triglycerides/TG,low-density lipoprotein cholesterol/LDL-C,high-density lipoprotein cholesterol/HDL-C),inflammatory cytokines(tumor necrosis factor-α/TNF-α,interleukin-1β/IL-1β,IL-6,monocyte chemoattractant protein-1/MCP-1),and oxidative stress markers(superoxide dismutase/SOD,malondialdehyde/MDA,gluta-thione peroxidase/GSH-Px)were measured.Aortic morphology and mitochondrial ultrastructure were evaluated by hematoxylin-eosin(HE)staining and transmission electron microscopy(TEM),respectively.The expression of autophagy-related proteins(Beclin-1,PINK1,Parkin,P62,LC3II/LC3I)was detected by Western blot(WB)and reverse transcription quantitative polymerase chain reaction(RT-qPCR).Results Compared with the model group,both the SGWDD and atorvastatin groups showed significant improvements:attenuated dyslipidemia(decreased TC,TG,and LDL-C;increased HDL-C),reduced levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,MCP-1),enhanced antioxidant capacity(increased SOD and GSH-Px;decreased MDA),and ameliorated aortic intimal thickening and lipid deposition.Furthermore,both treatments significantly promoted mitophagy,as evidenced by increased autophago-some formation,improved mitochondrial structure,upregulated protein and mRNA expression of Beclin-1,PINK1,Parkin,and LC3II/LC3I,and downregulated expression of P62(all P＜0.05).The effects of the two treatment groups were comparable.Conclusion SGWDD significantly ameliorates AS in ApoE-/-mice.The mechanism may be associated with the activation of the PINK1/Parkin-mediated mitophagy pathway,thereby reducing inflammatory response and oxidative stress.