Influence of artesunateon cardiomyocytenecroptosis induced by high glucose:an investigation based on RIP1/RIP3/MLKL signaling pathway
Zhou Suping
Wu Zhiyong
Yang Dezhong
Li Jinshun
Zhong Xu
Abstract：Objective To discuss the influence of artesunate (ART) on necroptosis of rat cardiomyocytes (H9c2 cells) induced by high glucose (HG) based on signaling pathway of receptor interacting protein kinase 1/receptor interacting protein kinase 3/mixed lineage kinase domain-like protein (RIP1/RIP3/MLKL).Methods H9c2 cells were treated with RIPK1 inhibitor-necrosstatin-1 and caspase inhibitor-Z-VAD-FMK to verify the programmed necrosis of H9c2 cells induced by HG.H9c2 cells were divided into normal group (NC group),HG group and low-dose,mid-dose and high-dose ART groups (L-ART group,M-ART group and H-ART group).The cell mortality,oxidative stress factors[lacticdehydrogenase (LDH),malondialdehyde (MDA),superoxide dismutase (SOD)],tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-1β (IL-1β),and protein expressions of phosphorylated RIP1 (p-RIP1),RIP1,phosphorylated RIP3 (p-RIP3),RIP3,phosphorylated MLKL (p-MLKL) and MLKL were detected respectively.Results ART could inhibit HG-induced programmed death of H9c2 cells.The results of Hoechst 33342/PI staining showed that ART could inhibit H9c2 necrotic death.The cell mortality,TNF-α,IL-6,IL-1β,LDH,MDA,and expressions of p-RIP1,p-RIP3 and p-MLKLdecreased significantly,and SOD activity increased significantly in L-ART group,M-ART group and H-ART groupcompared with HG group(P＜0.05).Conclusion ART can inhibit the necroptosis of cardiomyocytes induced by HG through restraining signaling pathway of RIP1/RIP3/MLKL in rats.
Keywords：CardiomyocytesRatsArtesunateReceptor interacting protein kinase 1/receptor interacting protein kinase 3/mixed lineage kinase domain-like protein
Publication Date：2024-12-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1491-1495 )