WIN55212-2 alleviates acute kidney injury in septic mice by regulating the AKT/mTOR/PFKFB3 signaling pathway

Xupeng DONG; Qianwen DUAN; Yuan MA; Che LIU; Yu GONG; Yuqing MA

doi:10.16016/j.2097-0927.202307071

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WIN55212-2 alleviates acute kidney injury in septic mice by regulating the AKT/mTOR/PFKFB3 signaling pathway

Basic Medicine | 更新时间：2026-01-09

- WIN55212-2 alleviates acute kidney injury in septic mice by regulating the AKT/mTOR/PFKFB3 signaling pathway
- Journal of Army Medical University Vol. 46, Issue 10, Pages: 1100-1106(2024)
- 作者机构：
  
  1.730000 兰州，兰州大学：第一临床医学院
  2.730000 兰州，兰州大学：第一医院麻醉科
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Gansu Province(21JRIRA077)
- DOI：10.16016/j.2097-0927.202307071
  CLC： R631.2;R692;R977.9
- Received：17 July 2023，
  
  Revised：2023-09-25，
  
  Published：30 May 2024
- 稿件说明：
移动端阅览
Xupeng DONG, Qianwen DUAN, Yuan MA, et al. WIN55212-2 alleviates acute kidney injury in septic mice by regulating the AKT/mTOR/PFKFB3 signaling pathway[J]. Journal of Army Medical University, 2024, 46(10): 1100-1106.
DOI：

Xupeng DONG, Qianwen DUAN, Yuan MA, et al. WIN55212-2 alleviates acute kidney injury in septic mice by regulating the AKT/mTOR/PFKFB3 signaling pathway[J]. Journal of Army Medical University, 2024, 46(10): 1100-1106. DOI： 10.16016/j.2097-0927.202307071.

摘要

目的

探讨大麻素受体激动剂WIN55212-2(WIN)对脓毒症小鼠急性肾损伤(acute kidney injury，AKI)的影响及其作用机制。

方法

24只雄性健康小鼠分为4组(

=6): 对照组(Control组)、脓毒症组(LPS组)、脓毒症+WIN55212-2组(LPS+WIN组)和脓毒症+WIN55212-2+mTOR激活剂MHY1485组(LPS+WIN+MHY组)。采用腹腔注射脂多糖(lipopolysaccharide，LPS)的方法构建脓毒症模型，造模24 h后取材，ELISA测定肾脏组织IL-1β、IL-18和乳酸脱氢酶A(lactate dehydrogenase A，LDHA)的含量以及血清Scr、肾损伤分子-1(kidney injury molecule-1，KIM-1)和乳酸

的含量；HE染色观察肾脏组织病理改变并进行Paller评分，Western blot检测肾脏组织p-AKT、p-mTOR及6-磷酸果糖激酶-2/果糖-2

6-二磷酸酶3(6-phosphofructo-2-kinase/fructose-2

6-biphosphatase 3，PFKFB3)的表达。

结果

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

0.05)，血清乳酸、Scr、KIM-1含量升高(

0.05)，肾脏组织LDHA、IL-1β、IL-18含量上调(

0.05)，肾脏组织p-AKT、p-mTOR、PFKFB3表达增加(

0.05)。与LPS组相比，LPS+WIN组肾脏组织病理损伤减轻，Paller评分降低(

0.05)，乳酸、Scr、KIM-1的含量降低(

0.05)，LDHA、IL-1β、IL-18含量下调(

0.05)，p-AKT、p-mTOR、PFKFB3表达减少(

0.05)。与LPS+WIN组相比，LPS+WIN+MHY组Paller评分升高(

0.05)，乳酸、Scr、KIM-1的含量升高(

0.05)，LDHA、IL-1β、IL-18含量上调(

0.05)，p-AKT、p-mTOR、PFKFB3表达增加(

0.05)。

结论

WIN可以减轻脓毒症AKI，其机制可能是通过抑制AKT/mTOR/PFKFB3信号通路，降低肾脏组织糖酵解水平，减轻炎症反应。

Abstract

Objective

To investigate the effects of cannabinoid receptor agonist

WIN55212-2 (WIN)

on acute kidney injury (AKI) in mice with sepsis and its underlying mechanism.

Methods

Twenty-four healthy male mice were divided into (

=6): Control group

sepsis group (LPS group)

sepsis+WIN55212-2 group (LPS+WIN group) and sepsis+WIN55212-2+mTOR activator MHY1485 group (LPS+WIN+MHY group). The sepsis model was constructed by intraperitoneal injection of LPS. After the tissue and blood samples were harvested in 24 h after modeling

ELISA was used to determine the contents of IL-1β

IL-18 and lactate dehydrogenase A (LDHA) in the renal tissues

as well as Scr

kidney injury molecule-1 (KIM-1) and lactic acid (LA) in the serum. HE staining was employed to observe the pathological changes of kidney tissue and Paller score was calculated. The expression of p-AKT

p-mTOR and 6-phosphofructokinase-2/fructose-2

6-biphosphatase 3 (PFKF

B3) in the renal tissues was detected by Western blotting.

Results

Compared with the Control group

the LPS group had obvious kidney tissue damage

increased Paller score (

0.05)

increased serum contents of lactic acid

Scr and KIM-1 (

0.05)

up-regulated contents of LDHA

IL-1β and IL-18 in the renal tissues (

0.05)

and elevated expression levels of p-AKT

p-mTOR and PFKFB3 in the renal tissues (

0.05). Milder pathological injury in kidney tissue

decreased Paller score (

0.05)

reduced contents of lactic acid

Scr and KIM-1 (

0.05)

decreased contents of LDHA

IL-1β and IL-18 (

0.05)

and lower expression of p-AKT

p-mTOR and PFKFB3 were observed in the LPS+WIN group than the LPS group (

0.05). The LPS+WIN+MHY group had notably higher Paller score (

0.05)

raised contents of lactic acid

Scr and KIM-1 (

0.05)

increased contents of LDHA

IL-1β and IL-18 (

0.05)

and up-regulated expression of p-AKT

p-mTOR and PFKFB3 (

0.05) when compared with the LPS+WIN group.

Conclusion

WIN can alleviate AKI in sepsis

and it may reduce the level of glycolysis in renal tissue

and alleviate inflammation through inhibiting AKT/mTOR/PFKFB3 signaling pathway.

关键词

Keywords

references

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