Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: gypenosides, lipopolysaccharide, acute lung injury, inflammatory response, apoptosis


中文翻译：

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Gypenosides 抑制 LPS 诱导的 ALI 中内皮和上皮细胞的炎症反应和凋亡：基于生物信息学分析和体内/体外实验的研究

引言：严重的炎症反应导致急性肺损伤（ALI）预后不良，绞股蓝皂苷（GPs）对ALI的作用尚不完全清楚。该研究旨在调查全科医生对 ALI 的影响。
方法：我们首先建立了LPS诱导的ALI小鼠模型。然后，我们测试了 GPs 是否有助于减轻体内 ALI 的炎症反应和肺损伤。为了确定该现象的具体机制，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，以识别中枢差异表达基因 (DEG)。DEGs 的 PPI 网络用于寻找中心基因。基于 DAVID 数据库进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 分析，以确定基因富集的途径。然后，我们测试了 GPs 是否通过丰富的途径抑制肺损伤和炎症反应。我们还测试了 GPs 是否抑制继发于严重炎症的内皮细胞和上皮细胞的凋亡。
结果：我们发现 GPs 显着减轻了肺损伤并提高了 LPS 诱导的 ALI 小鼠的体内存活率。生物信息学分析从 DEG 中鉴定出 20 个中枢基因，它们主要富集于 NF-κB 和 TNF-α 通路。GPs可以通过抑制体内NF-κB和TNF-α通路来减轻肺损伤和炎症反应。我们的结果表明，GPs 在体外还通过 NF-κB 和 TNF-α 通路抑制上皮细胞和内皮细胞的炎症反应。严重的炎症反应也可能导致内皮细胞和上皮细胞凋亡。我们的结果表明，GPs有效地抑制了内皮细胞和上皮细胞的凋亡。
结论：我们的研究表明，GPs有助于减轻体内肺损伤，并在体外抑制内皮细胞和上皮细胞的炎症和凋亡，为ALI的预防和治疗提供了新的策略。

关键词：绞股蓝皂苷，脂多糖，急性肺损伤，炎症反应，细胞凋亡