Emergency Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai 200071, China.
Hospital Infection Management Department, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai 200052, China.
Mediators Inflamm. 2023 Jul 27;2023:1257615. doi: 10.1155/2023/1257615. eCollection 2023.
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 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 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.
脓毒症的死亡率和发病率因急性肺损伤（ALI）或急性呼吸窘迫综合征而加重。已发表的研究发现，金丝桃苷（HYP）在许多疾病中具有抗炎和治疗作用。然而，HYP 治疗是否能减轻脓毒症引起的 ALI 仍不清楚。
本研究构建了盲肠结扎穿孔（CLP）诱导的脓毒症小鼠模型。采用蛋白质组学、免疫组织化学、免疫荧光和酶联免疫吸附试验检测促炎细胞因子，分析小鼠肺组织。用脂多糖（LPS）诱导人肺微血管内皮细胞（HLMVEC）建立模型。
结果表明，HYP 治疗通过提高存活率、降低炎症因子表达和肺组织细胞凋亡来减轻脓毒症引起的 ALI。同时，HYP 预处理恢复了 CLP 诱导的小鼠肺组织中的血管生成。蛋白质组学检测表明，Atg13 在 HYP 介导的脓毒症诱导的 ALI 保护中起关键作用。实验表明，HYP 通过调节 Atg13 介导的自噬来减轻 LPS 诱导的 HLMVEC 损伤。抑制自噬或沉默 Atg13 逆转了 HYP 对脓毒症诱导的 ALI 的保护作用。
综上所述，我们得出结论，HYP 通过调节自噬和抑制炎症来减轻脓毒症引起的 ALI。
