School of Biology and Food Engineering, Institute of Pharmaceutical Pharmacology Research Center, Suzhou University, Suzhou, Anhui, China.
Aging (Albany NY). 2023 Apr 5;15(14):6710-6720. doi: 10.18632/aging.204628.
Sepsis, a common critical disease, has high morbidity and mortality. Acute lung injury (ALI) is one of the important complications of sepsis, its effective treatment measures remain scarce. The purpose of the present study was to search for the biomarker and effective treatment measures. Lipopolysaccharide (LPS) was used to establish sepsis induced ALI model and . Proteomics, immunoprecipitation, molecular docking techniques, and Sirt3 knockout (KO) mice and silence MLE-12 cells were used to search for biomarker and treatment measures for sepsis ALI. 38 differentially expressed proteins were found in the lung tissues of sepsis ALI mice, among which Sirt3 changed most. Further study found that Sirt3 could inhibit NLRP3 activation. Sirt3 KO or silence significantly aggravated sepsis induced ALI and MLE-12 cell injury. Plantainoside D (PD), an effective component of , significantly improved sepsis induced ALI by regulation of Sirt3/NLRP3 pathway. In conclusion, Sirt3 may be the important molecular targets for sepsis ALI. PD could protect sepsis ALI via Sirt3/NLRP3 signal pathway. The findings provide a new treatment target for sepsis ALI and a potential treatment measure.
脓毒症是一种常见的危重病，具有较高的发病率和死亡率。急性肺损伤（ALI）是脓毒症的重要并发症之一，其有效的治疗措施仍然匮乏。本研究旨在寻找生物标志物和有效的治疗措施。脂多糖（LPS）用于建立脓毒症诱导的 ALI 模型，使用蛋白质组学、免疫沉淀、分子对接技术以及 Sirt3 敲除（KO）小鼠和沉默 MLE-12 细胞来寻找脓毒症 ALI 的生物标志物和治疗措施。在脓毒症 ALI 小鼠的肺组织中发现了 38 个差异表达的蛋白质，其中 Sirt3 变化最大。进一步的研究发现，Sirt3 可以抑制 NLRP3 的激活。Sirt3 KO 或沉默显著加重了脓毒症诱导的 ALI 和 MLE-12 细胞损伤。荭草苷 D（PD）是贯叶连翘的有效成分之一，通过调节 Sirt3/NLRP3 通路显著改善了脓毒症诱导的 ALI。总之，Sirt3 可能是脓毒症 ALI 的重要分子靶点。PD 通过 Sirt3/NLRP3 信号通路来保护脓毒症 ALI。这些发现为脓毒症 ALI 提供了新的治疗靶点和潜在的治疗措施。
