Hyperoside Attenuates Sepsis-Induced Acute Lung Injury (ALI) through Autophagy Regulation and Inflammation Suppression.

Abstract

Sepsis mortality and morbidity are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome. Published studies have discovered that hyperoside (HYP) has an anti-inflammatory and therapeutic effect in many diseases. However, whether HYP treatment can attenuate sepsis-induced ALI is still obscure. In this study, a cecal ligation and puncture (CLP)-induced sepsis mouse model was constructed. The mouse lungs were harvested and assessed using proteomics, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay for pro-inflammatory cytokines. Human lung microvascular endothelial cells (HLMVECs) were induced with lipopolysaccharide (LPS) for the in vitro model. The results showed that HYP treatment attenuated sepsis-induced ALI through an increased survival rate, decreased inflammatory factor expression, and lung tissue apoptosis. At the same time, HYP pretreatment restored angiogenesis in CLP-induced mouse lung tissues. Proteomics detection showed that Atg13 played a vital role in HYP-mediated protection against sepsis-induced ALI. The in vitro experiment showed HYP treatment attenuated LPS-induced HLMVEC damage by regulating Atg13-mediated autophagy. Inhibiting autophagy or silencing Atg13 reversed the protective effect of HYP against sepsis-induced ALI. Taken together, we conclude that HYP attenuated sepsis-induced ALI by regulating autophagy and inhibiting inflammation.