Salidroside mediates the p38 MAPK signaling pathway to inhibit LPS-induced pyrodeath and oxidative damage of cardiomyocytes

WANG Ming-yan; XUAN Qing-qing; XU Ling

doi:10.13820/j.cnki.gdyx.20231824

Abstract：Objective To investigate the regulatory effects of salidroside on lipopolysaccharide(LPS)-induced pyrodeath and oxidative damage and p38 mitogen-activated protein kinase(p38 MAPK)signaling pathway in rat cardio-myocytes.Methods Rat cardiac H9C2 cells were cultured in vitro and divided into different groups,including the con-trol group,LPS group,LPS+10 μmol/L salidroside group,LPS+20 μmol/L salidroside group,LPS+40 μmol/L sali-droside group,LPS+80 μmol/L salidroside group.After selecting the optimal concentration of salidroside,the groups were further divided into control,LPS,LPS+20 μmol/L salidroside,SB203580(a p38 MAPK signaling pathway inhibi-tor)group,LPS+20 μmol/L salidroside+SB203580 group,and LPS+20 μmol/L salidroside+C16-PAF(a p38 MAPK pathway activator)group.After 24 hours of intervention,enzyme-linked immunosorbent assay(ELISA)was used to measure the expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD).Cell viability was determined using the Cell Counting Kit-8(CCK-8).Real-time fluorescence quantitative PCR was employed to assess the mRNA expression of Cyclin D1 and Caspase-3.Western blotting was conducted to determine the protein expression levels of p38 MAPK signaling pathway-related pro-teins,Cyclin D1,Caspase-3,Caspase-1,Gasdermin-D(GSDMD),and NLR family pyrin domain-containing 3(NLRP3).Results Compared to the control group,the LPS group exhibited significantly increased levels of IL-6 and TNF-α,along with significantly decreased cell viability(P＜0.05).In comparison to the LPS group,the LPS+20,40,and 80 μmol/L salidroside groups showed significantly reduced IL-6 and TNF-α levels(P＜0.05),while the LPS+20 μmol/L salidroside group demonstrated significantly increased cell viability(P＜0.05).Consequently,the LPS+20 μmol/L salidroside group,which displayed anti-inflammatory effects and improved cell viability,was selected for subsequent experiments involving the p38 MAPK signaling pathway inhibitor SB203580 and the activator C16-PAF.Conclusion Salidroside effectively inhibits pyroptosis,oxidative stress,and apoptosis in LPS-induced rat cardiac H9C2 cells,promoting cell proliferation.This effect is likely associated with the inhibition of the p38 MAPK signaling pathway.