Back to Search
Start Over
[Role and mechanism of ginsenoside Rg1 in ameliorating sepsis-induced acute lung injury based on PERK/eIF2α/ATF4/CHOP-induced alveolar epithelial cell apoptosis].
- Source :
-
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica [Zhongguo Zhong Yao Za Zhi] 2024 Jul; Vol. 49 (14), pp. 3837-3847. - Publication Year :
- 2024
-
Abstract
- The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.
- Subjects :
- Animals
Mice
Male
Humans
Endoplasmic Reticulum Stress drug effects
Mice, Inbred C57BL
Acute Lung Injury drug therapy
Acute Lung Injury metabolism
Acute Lung Injury genetics
Ginsenosides pharmacology
Activating Transcription Factor 4 metabolism
Activating Transcription Factor 4 genetics
Apoptosis drug effects
Transcription Factor CHOP metabolism
Transcription Factor CHOP genetics
Sepsis drug therapy
Sepsis complications
Sepsis metabolism
Sepsis genetics
eIF-2 Kinase metabolism
eIF-2 Kinase genetics
Eukaryotic Initiation Factor-2 metabolism
Eukaryotic Initiation Factor-2 genetics
Alveolar Epithelial Cells drug effects
Alveolar Epithelial Cells metabolism
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1001-5302
- Volume :
- 49
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
- Publication Type :
- Academic Journal
- Accession number :
- 39099357
- Full Text :
- https://doi.org/10.19540/j.cnki.cjcmm.20240314.401