Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway

Objective‍‍ ‍To investigate the role and mechanism of paeoniflorin (PF) in sepsis-associated acute kidney injury (SA-AKI) in mice. Methods‍ ‍Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS. Twenty-four male C57BL/6J mice (6~8 weeks old, weighing 20~25 g) were randomly...

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Main Authors: GONG Yu, LEI Jiao, ZHANG Ming
Format: Article
Language:zho
Published: Editorial Office of Journal of Army Medical University 2025-01-01
Series:陆军军医大学学报
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Online Access:https://aammt.tmmu.edu.cn/html/202406099.html
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author GONG Yu
LEI Jiao
ZHANG Ming
author_facet GONG Yu
LEI Jiao
ZHANG Ming
author_sort GONG Yu
collection DOAJ
description Objective‍‍ ‍To investigate the role and mechanism of paeoniflorin (PF) in sepsis-associated acute kidney injury (SA-AKI) in mice. Methods‍ ‍Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS. Twenty-four male C57BL/6J mice (6~8 weeks old, weighing 20~25 g) were randomly divided into Control group, model group, PF group (intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration), and β-catenin specific agonist BML284 group (10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration). The renal histopathological changes were observed by HE staining and Paller scoring. ELISA was used to determine the contents of serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and lactate, and renal contents of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), IL-1β and IL-18. Western blotting was performed to detect the expression of total β-catenin, p-β-cateninY654, nucleus β-catenin and c-Myc. Results‍ ‍Compared with the Control group, the LPS group showed obviously damaged renal tissue, higher Paller score (P<0.05), increased serum Scr and NGAL levels (P<0.05), elevated renal contents of aerobic glycolytic indexes such as HK2, LDHA and serum lactate, as well as contents of IL-1β and IL-18 (P<0.05), and enhanced expression of total β-catenin, p-β-cateninY654, nucleus β-catenin and c-Myc in the renal tissue (P<0.05). PF treatment attenuated the renal tissue damage, decreased Paller score (P<0.05), reduced serum Scr and NGAL levels (P<0.05), HK2, LDHA and serum lactate levels, and contents of IL-1β and IL-18 in renal tissues (P<0.05), and down-regulated the renal expression of total β-catenin, p-β-cateninY654, nucleus β-catenin and c-Myc when compared with the levels in the model group (P<0.05). While, addition of BML284 reversed above effects of PF treatment with significant differences (P<0.05). Conclusion‍ ‍PF can alleviate SA-AKI, and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway, thus reducing the aerobic glycolysis level and inflammatory response in renal tissue. [‍
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spelling doaj-art-d37d1016865b476996557a444dd81fce2025-01-23T08:02:51ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272025-01-0147213214010.16016/j.2097-0927.202406099Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathwayGONG Yu0 LEI Jiao1ZHANG Ming2First Clinical Medical CollegeFirst Clinical Medical CollegeFirst Clinical Medical CollegeObjective‍‍ ‍To investigate the role and mechanism of paeoniflorin (PF) in sepsis-associated acute kidney injury (SA-AKI) in mice. Methods‍ ‍Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS. Twenty-four male C57BL/6J mice (6~8 weeks old, weighing 20~25 g) were randomly divided into Control group, model group, PF group (intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration), and β-catenin specific agonist BML284 group (10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration). The renal histopathological changes were observed by HE staining and Paller scoring. ELISA was used to determine the contents of serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and lactate, and renal contents of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), IL-1β and IL-18. Western blotting was performed to detect the expression of total β-catenin, p-β-cateninY654, nucleus β-catenin and c-Myc. Results‍ ‍Compared with the Control group, the LPS group showed obviously damaged renal tissue, higher Paller score (P<0.05), increased serum Scr and NGAL levels (P<0.05), elevated renal contents of aerobic glycolytic indexes such as HK2, LDHA and serum lactate, as well as contents of IL-1β and IL-18 (P<0.05), and enhanced expression of total β-catenin, p-β-cateninY654, nucleus β-catenin and c-Myc in the renal tissue (P<0.05). PF treatment attenuated the renal tissue damage, decreased Paller score (P<0.05), reduced serum Scr and NGAL levels (P<0.05), HK2, LDHA and serum lactate levels, and contents of IL-1β and IL-18 in renal tissues (P<0.05), and down-regulated the renal expression of total β-catenin, p-β-cateninY654, nucleus β-catenin and c-Myc when compared with the levels in the model group (P<0.05). While, addition of BML284 reversed above effects of PF treatment with significant differences (P<0.05). Conclusion‍ ‍PF can alleviate SA-AKI, and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway, thus reducing the aerobic glycolysis level and inflammatory response in renal tissue. [‍https://aammt.tmmu.edu.cn/html/202406099.htmlsepsis-associated acute kidney injurypaeoniflorinaerobic glycolysisβ-catenin/c-mycbml284
spellingShingle GONG Yu
LEI Jiao
ZHANG Ming
Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
陆军军医大学学报
sepsis-associated acute kidney injury
paeoniflorin
aerobic glycolysis
β-catenin/c-myc
bml284
title Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
title_full Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
title_fullStr Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
title_full_unstemmed Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
title_short Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
title_sort paeoniflorin alleviates sepsis associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β catenin c myc pathway
topic sepsis-associated acute kidney injury
paeoniflorin
aerobic glycolysis
β-catenin/c-myc
bml284
url https://aammt.tmmu.edu.cn/html/202406099.html
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AT leijiao paeoniflorinalleviatessepsisassociatedacutekidneyinjuryinmicebyinhibitingaerobicglycolysisthroughthebcatenincmycpathway
AT zhangming paeoniflorinalleviatessepsisassociatedacutekidneyinjuryinmicebyinhibitingaerobicglycolysisthroughthebcatenincmycpathway