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Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury
OBJECTIVE: To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. METHODS: Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injec...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857912/ https://www.ncbi.nlm.nih.gov/pubmed/33575163 http://dx.doi.org/10.1155/2021/7178253 |
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author | Sun, Jie Wei, Shanzhai Zhang, Yilai Li, Jia |
author_facet | Sun, Jie Wei, Shanzhai Zhang, Yilai Li, Jia |
author_sort | Sun, Jie |
collection | PubMed |
description | OBJECTIVE: To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. METHODS: Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1β, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. RESULTS: In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner (P < 0.05); the concentrations of BUN and Scr were increased (all P < 0.05); similarly, the levels of TNF-α and IL-1β were increased as well (all P < 0.05). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 μg/mL, it had no cytotoxicity in HK-2 cells, and 100 μg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS (P < 0.05). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 β, IL-6, and IL-8 (all P < 0.05), reducing the number of apoptotic cells (P < 0.05), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. CONCLUSION: APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT. |
format | Online Article Text |
id | pubmed-7857912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-78579122021-02-10 Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury Sun, Jie Wei, Shanzhai Zhang, Yilai Li, Jia Anal Cell Pathol (Amst) Research Article OBJECTIVE: To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. METHODS: Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1β, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. RESULTS: In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner (P < 0.05); the concentrations of BUN and Scr were increased (all P < 0.05); similarly, the levels of TNF-α and IL-1β were increased as well (all P < 0.05). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 μg/mL, it had no cytotoxicity in HK-2 cells, and 100 μg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS (P < 0.05). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 β, IL-6, and IL-8 (all P < 0.05), reducing the number of apoptotic cells (P < 0.05), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. CONCLUSION: APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT. Hindawi 2021-01-26 /pmc/articles/PMC7857912/ /pubmed/33575163 http://dx.doi.org/10.1155/2021/7178253 Text en Copyright © 2021 Jie Sun et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Sun, Jie Wei, Shanzhai Zhang, Yilai Li, Jia Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury |
title | Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury |
title_full | Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury |
title_fullStr | Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury |
title_full_unstemmed | Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury |
title_short | Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury |
title_sort | protective effects of astragalus polysaccharide on sepsis-induced acute kidney injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857912/ https://www.ncbi.nlm.nih.gov/pubmed/33575163 http://dx.doi.org/10.1155/2021/7178253 |
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