人参皂苷Rg1通过调控自噬对小鼠心脏衰老的作用机制研究OACHSSCD

Objective:To investigate the mechanisms by which ginsenoside Rg1 regulates autophagy via the mammalian target of rapamycin/p70 ribosomal protein S6 kinase/eukaryotic translation initiation factor 4E-binding protein 1(mTOR/p70S6K/4EBP1)signaling pathway in cardiac aging in mice.Methods:Mice were divided into four groups.Eight C57BL/6J 8-week-old male mice served as the young control group(Con),and 24 C57BL/6J 16-month-old male mice were randomly divided into a natural aging model group(Mod),a rapamycin group(Rap),and a ginsenoside Rg1 group(Rg1),with 8 mice in each group.After 6 weeks of in-tragastric administration,frailty scores were used to evaluate aging status in each group.Cardiac function was assessed by echocar-diography.Hematoxylin-eosin(HE)staining and Masson's trichrome staining were used to observe myocardial morphology and col-lagen fiber deposition.Immunohistochemistry and RT-PCR were performed to detect pathological changes and mRNA expression ofα-smooth muscle actin(α-SMA),collagen type Ⅰ(Collagen Ⅰ),collagen type Ⅲ(Collagen Ⅲ),tumor protein p53(p53),and cyclin-dependent kinase inhibitor 1A(p21).Western blot analysis was used to detect the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ(LC3 Ⅱ/Ⅰ),p62,Beclin-1,and proteins in the mTOR/p70S6K/4EBP1 sig-naling pathway.Results:Frailty scores showed that the Mod group exhibited the highest degree of aging,while both the Rap and Rg1 groups showed significant improvement.Echocardiography demonstrated that cardiac function in the Rap and Rg1 groups was significantly improved compared with the Mod group.HE staining showed reduced myocardial degeneration and necrosis in the Rap and Rg1 groups.Masson's trichrome staining and immunohistochemistry indicated that myocardial fibrosis and aging were alleviated in the Rap and Rg1 groups,which was further confirmed by RT-PCR showing decreased mRNA expression levels of related markers to varying degrees.Western blot analysis showed that p62 expression was significantly decreased,while LC3 Ⅱ/Ⅰ and Beclin-1 were upregulated in the Rap and Rg1 groups.In addition,phosphorylation levels of mTOR,p70S6K,and 4EBP1 were downregulated to varying degrees.Conclusion:Ginsenoside Rg1 can effectively delay cardiac aging in naturally aged mice and improve myocardial fibrosis.Its mechanism may be associated with enhanced autophagy via the mTOR/p70S6K/4EBP1 signaling pathway.