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

GONG Yu; LEI Jiao; ZHANG Ming; XIE Jing; LI Ruonan; MA Yuqing

doi:10.16016/j.2097-0927.202406099

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

Basic Medicine | 更新时间：2025-01-23

- Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway
- Journal of Army Medical University Vol. 47, Issue 2, Pages: 132-140(2025)
- 作者机构：
  
  1.兰州大学，第一临床医学院，甘肃兰州
  2.兰州大学，第一医院麻醉科，甘肃兰州
- 作者简介：
  
  MA Yuqing， E-mail： myq2392466@163.com
- 基金信息：
  
  founder：Supported by the Natural Science Foundation of Gansu Province(24JRRA1075);the Fund of the First Hospital of Lanzhou University(ldyyyn2022-5)
- DOI：10.16016/j.2097-0927.202406099
  CLC： R285.5;R631;R692
- Published：30 January 2025，
  
  Received：01 July 2024，
  
  Revised：08 September 2024，
- 稿件说明：
移动端阅览
GONG YU, LEI JIAO, ZHANG MING, et al. Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway. [J]. Journal of army medical university, 2025, 47(2): 132-140.
DOI：

GONG YU, LEI JIAO, ZHANG MING, et al. Paeoniflorin alleviates sepsis-associated acute kidney injury in mice by inhibiting aerobic glycolysis through the β-catenin/c-Myc pathway. [J]. Journal of army medical university, 2025, 47(2): 132-140. DOI： 10.16016/j.2097-0927.202406099.

摘要

目的

探究芍药苷（paeoniflorin，PF）在小鼠脓毒症相关急性肾损伤（sepsis-associated acute kidney injury， SA-AKI）中的作用及机制。

方法

采用腹腔注射脂多糖（lipopolysaccharide， LPS）的方法构建小鼠SA-AKI模型。将24只6~8周龄的雄性C57BL/6J小鼠（体质量为20~25 g），用随机数字表法分为4组（

=6）：对照组（Control组）；模型组（LPS组），腹腔注射LPS（15 mg/kg）；芍药苷组（LPS+PF组），LPS造模前30 min腹腔注射PF（50 mg/kg）；β-catenin特异性激动剂BML284组（LPS+PF+BML284组），LPS造模前30 min，先腹腔注射PF（50 mg/kg），再腹腔注射BML284（10 mg/kg）。采用HE染色观察肾脏组织病理变化并进行Paller评分；采用ELISA检测血清肌酐（serum creatinine， Scr）、中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin，NGAL）和乳酸，以及肾组织己糖激酶2（hexokinase2，HK2）、乳酸脱氢酶A（lactate dehydrogenase A，LDHA）、白细胞介素-1β（interleukin-1β，IL-1β）和白细胞介素18（interleukin-18，IL-18）的含量；Western blot检测总β-

连环蛋白（beta-catenin， β-catenin）、磷酸化β-catenin

Y654

（p-β-catenin

Y654

）、细胞核β-catenin以及c-骨髓细胞瘤癌基因蛋白（c-myelocytomatosis oncogene gene， c-Myc）的表达。

结果

与Control组比较，LPS组HE染色显示肾脏组织受损，Paller评分升高（

0.05），血清Scr、NGAL增加（

0.05），肾组织HK2、LDHA及血清乳酸等有氧糖酵解指标和IL-1β、IL-18含量增多（

0.05），肾组织总β-catenin、p-β-catenin

Y654

、细胞核β-catenin以及c-Myc表达上升（

0.05）。与LPS组相比，LPS+PF组HE染色显示肾脏组织损伤减轻，Paller评分下降（

0.05），血清Scr、NGAL降低（

0.05），肾组织HK2、LDHA及血清乳酸等有氧糖酵解指标和IL-1β、IL-18含量减少（

0.05），肾组织总β-catenin、p-β-catenin

Y654

、细胞核β-catenin以及c-Myc表达下调（

0.05）。与LPS+PF组比较，LPS+PF+BML284组HE染色显示肾脏组织受损加重，Paller评分升高（

0.05），血清Scr、NGAL增加（

0.05），肾组织HK2、LDHA及血清乳酸等有氧糖酵解指标和IL-1β、IL-18含量增多（

0.05），肾组织总β-catenin、p-β-catenin

Y654

、细胞核β-catenin以及c-Myc表达上升（

0.05）。

结论

PF可以缓解SA-AKI，其机制可能是通过抑制β-catenin/c-Myc通路，降低肾组织有氧糖酵解水平和炎症反应。

Abstract

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-catenin

Y654

， nucleus β-catenin and c-Myc. Results‍　‍Compared with the Control group， the LPS group showed obviously damaged renal tissue， higher Paller score （

0.05）， increased serum Scr and NGAL levels （

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 （

0.05）， and enhanced expression of total β-catenin， p-β-catenin

Y654

， nucleus β-catenin and c-Myc in the renal tissue （

0.05）. PF treatment attenuated the renal tissue damage， decreased Paller score （

0.05）， reduced serum Scr and NGAL levels （

0.05）， HK2， LDHA and serum lactate levels， and contents of IL-1β and IL-18 in renal tissues （

0.05）， and down-regulated the renal expression of total β-catenin， p-β-catenin

Y654

， nucleus β-catenin and c-Myc when compared with the levels in the model group （

0.05）. While， addition of BML284 reversed above effects of PF treatment with significant differences （

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.

关键词

脓毒症相关急性肾损伤芍药苷有氧糖酵解β-catenin/c-Myc通路BML284

Keywords

sepsis-associated acute kidney injurypaeoniflorinaerobic glycolysisβ-catenin/c-MycBML284

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