IL‑5 alleviates acute kidney injury in septic mice by inhibiting the caspase‑1 pyroptosis signaling pathway

REN Yongdong; CHEN Hairui; HU Niandan; AI Bo; LI Wenqiang

doi:10.14188/j.1671-8852.2024.0867

您当前的位置：

首页 >

文章列表页 >

IL‑5 alleviates acute kidney injury in septic mice by inhibiting the caspase‑1 pyroptosis signaling pathway

更新时间：2026-11-05

- IL‑5 alleviates acute kidney injury in septic mice by inhibiting the caspase‑1 pyroptosis signaling pathway
- Medical Journal of Wuhan University Vol. 46, Issue 11, Pages: 1388-1393(2025)
- 作者机构：
  
  武汉大学人民医院急诊科湖北武汉 430060
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0867
  CLC： R34
- Received：11 November 2024，
  
  Published：25 November 2025
- 稿件说明：
移动端阅览
任永栋,陈海瑞,胡念丹等.IL‑5抑制caspase‑1细胞焦亡信号通路减轻脓毒症小鼠急性肾损伤[J].武汉大学学报（医学版）,2025,46(11):1388-1393.

REN Yongdong,CHEN Hairui,HU Niandan,et al.IL‑5 alleviates acute kidney injury in septic mice by inhibiting the caspase‑1 pyroptosis signaling pathway[J].Medical Journal of Wuhan University,2025,46(11):1388-1393.
任永栋,陈海瑞,胡念丹等.IL‑5抑制caspase‑1细胞焦亡信号通路减轻脓毒症小鼠急性肾损伤[J].武汉大学学报（医学版）,2025,46(11):1388-1393. DOI： 10.14188/j.1671-8852.2024.0867.

REN Yongdong,CHEN Hairui,HU Niandan,et al.IL‑5 alleviates acute kidney injury in septic mice by inhibiting the caspase‑1 pyroptosis signaling pathway[J].Medical Journal of Wuhan University,2025,46(11):1388-1393. DOI： 10.14188/j.1671-8852.2024.0867.

摘要

目的

探究白细胞介素‑5（IL‑5）对脓毒症所致小鼠急性肾损伤的影响及机制。

方法

盲肠结扎穿孔法（CLP）构建小鼠脓毒症急性肾损伤模型，40只小鼠随机分为假手术（Sham）组、脓毒症模型（CLP）组、IL‑5干预（CLP+IL‑5）组、假手术+IL‑5（Sham+IL‑5）组。造模后24 h取材，ELISA检测各组小鼠血清中肿瘤坏死因子‑α（TNF‑α）、IL‑6、IL‑1β、肌酐（Scr）、尿素氮（BUN）的含量；HE染色观察肾脏病理学改变；TUNEL染色检测肾组织细胞凋亡情况；Western Blot检测肾脏组织中NLRP3、caspase‑1蛋白表达。

结果

IL‑5减轻了脓毒症小鼠肾脏病理损伤程度，降低脓毒症小鼠血清中TNF‑α、IL‑6、IL‑1β、Scr、BUN的浓度及肾组织NLRP3、caspase‑1蛋白表达水平（

0.05），抑制细胞凋亡与炎症反应，改善脓毒症相关急性肾损伤。

结论

IL‑5能够抑制全身炎症反应，从而减轻脓毒症所致的急性肾损伤，其作用机制可能与IL‑5抑制NLRP3炎症小体的激活以及caspase‑1介导的经典细胞焦亡途径的活化相关。

Abstract

Objective

To explore the effects of interleukin⁃5 (IL⁃5) on sepsis⁃induced acute kidney injury in mice.

Methods

A mouse model of septic acute kidney injury was established using the cecal ligation and puncture (CLP) method. Forty mice were randomly assigned to four groups: Sham group

sepsis model (CLP) group

IL‑5 intervention (CLP+IL‑5) group

and Sham+IL‑5 group. Tissue samples were collected 24 hours post‑modeling. ELISA was utilized to measure serum levels of tumor necrosis factor‑alpha (TNF‑α)

IL‑6

IL‑1β

creatinine (Scr)

and blood urea nitrogen (BUN). HE staining was performed to evaluate renal tissue pathology

TUNEL staining to assess apoptosis

and Western Blot to determine NLRP3 and caspase‑1 proteins expression in kidney tissues.

Results

IL‑5 significantly attenuated renal histological injury in septic mice. It reduced serum levels of TNF‑α

IL‑6

IL‑1β

Scr

and BUN

and suppressed NLRP3 and caspase‑1 protein expression in kidney tissues (

0.05). By inhibiting apoptosis and the inflammatory response

IL‑5 markedly ameliorated sepsis⁃associated acute kidney injury.

Conclusion

IL‑5 inhibits the systemic inflammatory response

thereby mitigating acute kidney injury induced by sepsis. This protective effect may be mediated through the suppression of NLRP3 inflammasome activation and inhibition of the caspase‑1‑mediated classical pyroptosis pathway.

关键词

Keywords

references

EVANS L , RHODES A , ALHAZZANI W , et al . Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021 [J ] . Intensive Care Med , 2021 , 47 ( 11 ): 1181 ‑ 1247 .

PAIS T , JORGE S , LOPES J A . Acute kidney injury in sepsis [J ] . Int J Mol Sci , 2024 , 25 ( 11 ): 5924 .

ZARBOCK A , NADIM M K , PICKKERS P , et al . Sepsis‑associated acute kidney injury: Consensus report of the 28th Acute Disease Quality Initiative workgroup [J ] . Nat Rev Nephrol , 2023 , 19 : 401 ‑ 417 .

BAGSHAW S M , UCHINO S , BELLOMO R , et al . Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes [J ] . Clin J Am Soc Nephrol , 2007 , 2 ( 3 ): 431 ‑ 439 .

PEERAPORNRATANA S , MANRIQUE‑CABALLERO C L , GÓMEZ H , et al . Acute kidney injury from sepsis: Current concepts, epidemiology, pathophysiology, prevention and treatment [J ] . Kidney Int , 2019 , 96 ( 5 ): 1083 ‑ 1099 .

LI T L , SUN H B , LI Y M , et al . Downregulation of macrophage migration inhibitory factor attenuates NLRP3 inflammasome mediated pyroptosis in sepsis‑induced AKI [J ] . Cell Death Discov , 2022 , 8 : 61 .

沈灵芝 , 李莉 , 严静 . 白细胞介素‑5对脓毒症小鼠的保护作用研究 [J ] . 中华内科杂志 , 2019 , 58 ( 6 ): 456 ‑ 459 .

SHEN L Z , LI L , YAN J . The protective effect of interleukin‑5 in septic mice [J ] . Chin J Intern Med , 2019 , 58 ( 6 ): 456 ‑ 459 .

FOSTER P S , MALTBY S , ROSENBERG H F , et al . Modeling T H 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma [J ] . Immunol Rev , 2017 , 278 ( 1 ): 20 ‑ 40 .

DAMRON C L , BLOODWORTH J C , HOJI A , et al . Increased allergic inflammation and decreased lung insulin sensitivity in offspring of obese allergic mothers [J ] . J Leukoc Biol , 2024 , 116 ( 5 ): 985 ‑ 994 .

SHEN C , WU N , CHEN X , et al . Interleukin‑5 alleviates cardiac remodelling via the STAT3 pathway in angiotensin Ⅱ‑infused mice [J ] . J Cell Mol Med , 2024 , 28 ( 13 ): e18493 .

MOHYELDIN R H , ALAAELDIN R , SHARATA E E , et al . LCZ696 attenuates sepsis‑induced liver dysfunction in rats; the role of oxidative stress, apoptosis, and JNK1/2‑P38 signaling pathways [J ] . Life Sci , 2023 , 334 : 122210 .

PALLER M S , HOIDAL J R , FERRIS T F . Oxygen free radicals in ischemic acute renal failure in the rat [J ] . J Clin Invest , 1984 , 74 ( 4 ): 1156 ‑ 1164 .

KUWABARA S , GOGGINS E , OKUSA M D . The pathophysiology of sepsis‑associated AKI [J ] . Clin J Am Soc Nephrol , 2022 , 17 ( 7 ): 1050 ‑ 1069 .

POSTON J T , KOYNER J L . Sepsis associated acute kidney injury [J ] . BMJ , 2019 , 364 : k4891 .

ZARBOCK A , KOYNER J L , GOMEZ H , et al . Sepsis‑associated acute kidney injury‑treatment standard [J ] . Nephrol Dial Transplant , 2023 , 39 ( 1 ): 26 ‑ 35 .

LINCH S N , DANIELSON E T , KELLY A M , et al . Interleukin 5 is protective during sepsis in an eosinophil‑independent manner [J ] . Am J Respir Crit Care Med , 2012 , 186 ( 3 ): 246 ‑ 254 .

POLAT B , CADIRCI E , HALICI Z , et al . The protective effect of amiodarone in lung tissue of cecal ligation and puncture‑induced septic rats: A perspective from inflammatory cytokine release and oxidative stress [J ] . Naunyn Schmiedeberg's Arch Pharmacol , 2013 , 386 ( 7 ): 635 ‑ 643 .

WEI B , CHEN Y , ZHOU W , et al . Interleukin IL‑5 alleviates sepsis‑induced acute lung injury by regulating the immune response in rats [J ] . Bioengineered , 2021 , 12 ( 1 ): 2132 ‑ 2139 .

HERCUS T R , KAN W L T , BROUGHTON S E , et al . Role of the β common (βc) family of cytokines in health and disease [J ] . Cold Spring Harb Perspect Biol , 2018 , 10 ( 6 ): a028514 .

SHARAWY M H , SERRYA M S . Pirfenidone attenuates gentamicin‑induced acute kidney injury by inhibiting inflammasome‑dependent NLRP3 pathway in rats [J ] . Life Sci , 2020 , 260 : 118454 .

LI Z , WANG X , PENG Y , et al . Nlrp3 deficiency alleviates lipopolysaccharide‑induced acute kidney injury via suppressing renal inflammation and ferroptosis in mice [J ] . Biology (Basel) , 2023 , 12 ( 9 ): 1188 .

HAN S , LI S , LI J , et al . Hederasaponin C inhibits LPS‑induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF‑κB/NLRP3 signaling pathway [J ] . Phytother Res , 2023 , 37 ( 12 ): 5974 ‑ 5990 .

房尚萍 , 孙任珂 , 苏慧 , 等 . 绿原酸减轻脓毒症诱导的小鼠急性肾损伤: 基于抑制caspase‑1经典细胞焦亡信号通路 [J ] . 南方医科大学学报 , 2024 , 44 ( 2 ): 317 ‑ 323 .

FANG S P , SUN R K , SU H , et al . Chlorogenic acid alleviates acute kidney injury in septic mice by inhibiting NLRP3 inflammasomes and the caspase‑1 canonical pyroptosis pathway [J ] . J South Med Univ , 2024 , 44 ( 2 ): 317 ‑ 323 .

Views

222

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Serum uric acid is an independent risk factor for acute kidney injury in patients with sepsis

Protective Effect of Shenkang Injection Against Rats with Septic Acute Kidney Injury

Remimazolam versus midazolam for sedation in mechanically ventilated patients with sepsis

Effects of Hederagenin on cardiac hypertrophy and fibrosis induced by pressure overload in mice

Radiofrequency treatment for scalp rejuvenation in facial anti⁃aging

Related Author

REN Yongdong

CHEN Hairui

HU Niandan

AI Bo

LI Wenqiang

Maobi WEI

Zhiqin ZHANG

Xi BU

Related Institution

Dept.of Emergency， Renmin Hospital of Wuhan University

Dept. of Nephrology， Zhongnan Hospital of Wuhan University

Dept. of Nephrology， The Fourth Hospital of Changsha

Hubei Medical Association

Dept.of General Surgery,Qingpu Branch of Zhongshan Hospital,Fudan University

AI问答

⁰