Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China.
School of Anesthesiology, Weifang Medical University, Weifang 261053, People's Republic of China.
Drug Des Devel Ther. 2021 Jan 25;15:289-303. doi: 10.2147/DDDT.S286297. eCollection 2021.
Severe inflammatory response leads to poor prognosis of acute lung injury (ALI), the role of gypenosides (GPs) on ALI is not fully clear. The study aimed at investigating the effects of GPs on ALI.
We firstly established LPS-induced ALI mice model. Then, we tested whether GPs contributed to alleviate inflammatory response and lung injury of ALI in vivo. In order to identify specific mechanisms of the phenomenon, we conducted a bioinformatic analysis of LPS-induced ALI mice based on GEO database to identify hub differentially expressed genes (DEGs). PPI network of the DEGs was used to find hub-genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted based on the DAVID database to identify which pathways the genes enriched. Then, we tested whether GPs inhibited lung injury and inflammatory response via the enriched pathways. We also tested whether GPs inhibited the apoptosis of endothelial and epithelial cells secondary to severe inflammation.
We found GPs significantly alleviated lung injury and improved the survival rate of LPS-induced ALI mice in vivo. Bioinformatic analysis identified 20 hub-genes from DEGs, they were mainly enriched in NF-κB and TNF-α pathways. GPs could reduce the lung injury and inflammatory response via inhibiting NF-κB and TNF-α pathways in vivo. Our results indicated that GPs also inhibited inflammatory response of epithelial and endothelial cells via NF-κB and TNF-α pathways in vitro. Severe inflammatory response could also lead to apoptosis of endothelial and epithelial cells. Our results indicated that GPs effectively inhibited the apoptosis of endothelial and epithelial cells.
Our study suggested GPs contributed to alleviated lung injury in vivo and inhibited inflammation and apoptosis of endothelial and epithelial cells in vitro, providing novel strategies for the prevention and therapy for ALI.
严重的炎症反应导致急性肺损伤（ALI）预后不良，绞股蓝苷（GPs）在 ALI 中的作用尚不完全清楚。本研究旨在探讨 GPs 对 ALI 的影响。
我们首先建立了 LPS 诱导的 ALI 小鼠模型。然后，我们测试了 GPs 是否有助于缓解体内 ALI 的炎症反应和肺损伤。为了确定这种现象的具体机制，我们基于 GEO 数据库对 LPS 诱导的 ALI 小鼠进行了生物信息学分析，以鉴定差异表达基因（DEGs）的关键基因。使用 PPI 网络找到关键基因。基于 DAVID 数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，以确定基因富集的途径。然后，我们测试了 GPs 是否通过富集途径抑制肺损伤和炎症反应。我们还测试了 GPs 是否抑制严重炎症引起的内皮和上皮细胞凋亡。
我们发现 GPs 显著缓解了 LPS 诱导的 ALI 小鼠的肺损伤并提高了其存活率。生物信息学分析从 DEGs 中鉴定出 20 个关键基因，它们主要富集在 NF-κB 和 TNF-α 途径中。GPs 可以通过抑制体内 NF-κB 和 TNF-α 途径来减轻肺损伤和炎症反应。我们的结果表明，GPs 还可以通过 NF-κB 和 TNF-α 途径抑制上皮和内皮细胞的炎症反应。严重的炎症反应也会导致内皮和上皮细胞凋亡。我们的结果表明，GPs 有效地抑制了内皮和上皮细胞的凋亡。
我们的研究表明，GPs 有助于减轻体内肺损伤，并抑制体外内皮和上皮细胞的炎症和凋亡，为 ALI 的预防和治疗提供了新策略。
