扶正解毒颗粒经p38MAPK信号通路保护脓毒症大鼠心肌细胞的机制探究OA

Objective To investigate the protective effects of Fuzheng Jiedu Granules(FZJG)on cardiomyocytes in sepsis and to elucidate the underlying mechanism involving the p38 mitogen-activated protein kinase(p38MAPK)sig-naling pathway.Methods In the in vitro study,an inflammatory injury model was established by stimulating H9c2 car-diomyocytes with lipopolysaccharide(LPS).The safe concentration of FZJG was determined using the Cell Counting Kit-8(CCK-8)assay.Intracellular reactive oxygen species(ROS)production,inflammatory cytokine expression,and ap-optosis-related gene expression were evaluated following FZJG treatment.The p38MAPK inhibitor SB203580 was used in combination with FZJG to verify the underlying mechanism.In the in vivo study,a rat model of sepsis-induced cardiomy-opathy(SIC)was established by cecal ligation and puncture(CLP).Animals were randomly assigned to the control group,model group,low-,medium-,and high-dose FZJG groups,positive control group(levosimendan),and high-dose FZJG plus SB203580 group.Myocardial protective effects and modulation of the p38MAPK pathway were comprehen-sively evaluated by hematoxylin-eosin(HE)staining,measurement of serum myocardial injury biomarkers,oxidative stress indices,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blot analysis.Results In the in vitro study,the CCK-8 assay demonstrated that FZJG at concentrations ≤ 40 000 μg/mL maintained cell viability above 95％.Based on safety and efficacy considerations,10 000 μg/mL was selected as the optimal concentration for subsequent experiments.FZJG significantly reduced intracellular ROS production in LPS-stimulated H9c2 cells,downregulated the mRNA expression of IL-6,IL-1β,TNF-α,Bax,and Caspase-3,and upregulated Bel-2 mRNA expression.These protective effects were further enhanced by co-treatment with SB203580(all P＜0.05).In the in vivo study,medium-and high-dose FZJG significantly reduced serum levels of creatine kinase-MB(CK-MB),lactate dehydrogenase(LDH),and cardiac tropo-nin I(cTnI),alleviated myocardial histopathological injury,suppressed inflammatory cytokine expression,improved oxi-dative stress status by increasing superoxide dismutase(SOD)and glutathione(GSH)while reducing malondialdehyde(MDA),inhibited cardiomyocyte apoptosis,and decreased myocardial p38MAPK mRNA expression and protein phosphoryl-ation levels(all P＜0.05).Combined treatment with SB203580 produced synergistic cardioprotective effects.Conclusion Fuzheng Jiedu Granules exert significant protective effects against sepsis-induced myocardial injury.The underlying mecha-nism may involve inhibition of p38MAPK signaling pathway activation,thereby attenuating inflammatory responses,oxidative stress,and cardiomyocyte apoptosis.These findings provide experimental evidence supporting the development of FZJG as a multi-target traditional Chinese medicine formulation for the treatment of sepsis-induced cardiomyopathy.