Effect of BMAL1 on kidney injury in mice caused by sepsis

YANG Songyuan; YE Zehua; CHEN Wu; LI Wei; CHENG Fan

doi:10.14188/j.1671-8852.2024.0515

您当前的位置：

首页 >

文章列表页 >

Effect of BMAL1 on kidney injury in mice caused by sepsis

更新时间：2026-11-05

- Effect of BMAL1 on kidney injury in mice caused by sepsis
- Medical Journal of Wuhan University Vol. 46, Issue 9, Pages: 1113-1117(2025)
- 作者机构：
  
  武汉大学人民医院泌尿外科湖北武汉 430060
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0515
  CLC： R692.5
- Received：09 July 2024，
  
  Published：26 September 2025
- 稿件说明：
移动端阅览
杨淞源,叶泽华,陈伍等.BMAL1对脓毒血症致小鼠肾损伤的影响[J].武汉大学学报（医学版）,2025,46(09):1113-1117.

YANG Songyuan,YE Zehua,CHEN Wu,et al.Effect of BMAL1 on kidney injury in mice caused by sepsis[J].Medical Journal of Wuhan University,2025,46(09):1113-1117.
杨淞源,叶泽华,陈伍等.BMAL1对脓毒血症致小鼠肾损伤的影响[J].武汉大学学报（医学版）,2025,46(09):1113-1117. DOI： 10.14188/j.1671-8852.2024.0515.

YANG Songyuan,YE Zehua,CHEN Wu,et al.Effect of BMAL1 on kidney injury in mice caused by sepsis[J].Medical Journal of Wuhan University,2025,46(09):1113-1117. DOI： 10.14188/j.1671-8852.2024.0515.

摘要

目的

探讨BMAL1基因在脓毒血症所致小鼠急性肾损伤中的作用及机制。

方法

将20只雄性C57BL/6小鼠随机分为对照组（NC）、模型组（LPS）、空载病毒组（Vector）、BMAL1过表达‑LPS组（OE‑BMAL1+LPS），每组各5只。模型组小鼠腹腔注射脂多糖（20 mg·kg

-1

）构建脓毒血症急性肾损伤小鼠模型，空载病毒组使用尾静脉注射空载慢病毒，BMAL1过表达+LPS组小鼠在造模前20 d尾静脉注射过表达BMAL1的慢病毒，20 d后行腹腔注射脂多糖（20 mg·kg

-1

）。各组小鼠在造模后24 h取材并检测4组小鼠血清肌酐、尿素氮水平。取4组小鼠左侧肾脏组织，行HE染色观察肾脏组织损伤情况；行免疫荧光染色，观察肾组织KIM‑1和BMAL1表达情况；行Tunel染色，观察肾脏组织凋亡情况，采用Western Blot法检测肾组织BMAL1、KIM‑1、NGAL、Bcl‑2、Bax、PI3K、p‑PI3K、Akt及p‑Akt蛋白相对表达量。

结果

（1）模型组血清肌酐、尿素氮水平均高于对照组，而BMAL1过表达‑LPS组均低于对照组（

0.05）。（2）对照组肾组织结构正常，未见明显炎症细胞浸润；模型组肾组织出现严重的肾小管扩张或肿胀、空泡变性、炎性细胞浸润、肾小管局灶性坏死等明显的病理变化。与模型组相比，BMAL1过表达+LPS组肾组织肾小管损伤减轻，有少量炎性细胞浸润。（3）模型组肾组织KIM‑1、NGAL、Bax、p‑PI3K、PI3K、p‑Akt、Akt蛋白相对表达量均高于对照组，而BMAL1过表达+LPS组肾组织上述蛋白相对表达量均低于模型组。模型组肾脏BMAL1及Bcl‑2蛋白表达量均低于对照组；而BMAL1过表达+LPS组肾脏BMAL1及Bcl‑2蛋白表达量均高于模型组。

结论

BMAL1基因可以通过下调PI3K‑Akt通路，抑制细胞凋亡，从而发挥脓毒血症性急性肾损伤保护作用，过表达BMAL11基因可以减轻脓毒血症导致的急性肾损伤。

Abstract

Objective

To investigate the role and mechanism of BMAL1 in sepsis‑induced acute kidney injury (AKI) in mice.

Methods

Twenty male C57BL/6 mice were randomly divided into four groups with five mice in each group: control group (NC)

model group (lipopolysaccharide

LPS)

vector group (Vector)

and BMAL1 overexpression+LPS group (OE‑BMAL1+LPS). The model group mice were intraperitoneally injected with LPS( 20 mg·kg

-1

) to establish a sepsis‑induced AKI model

the vector group received intravenous injections of empty vector lentivirus

and the BMAL1 overexpression+LPS group mice were injected intravenously with BMAL1‑overexpressing lentivirus 20 days before modeling

followed by LPS injection（20 mg·kg

-1

）20 days later. Blood samples were taken 24 hours post‑modeling to measure serum creatinine and urea nitrogen levels. Kidney tissue from the left side of each mouse was collected for histological examination using hematoxylin and eosin staining

immunohistochemical staining to observe KIM‑1 and BMAL1 expression. TUNEL assay was adopted to observe the apoptosis in kidney tissue

and Western Blot was used to measure the relative expression of proteins BMAL1

KIM‑1

NGAL

Bcl‑2

Bax

PI3K

p‑PI3K

Akt

and p‑Akt in kidney tissues.

Results

(1) Serum creatinine and urea nitrogen levels in the model group were higher than that in the control group

while those in the BMAL1 overexpression+LPS group were lower （

0.05）. (2) The kidney tissue structure in control group was normal with no significant inflammatory cell infiltration; while the model group exhibited severe pathological changes including tubular dilation or swelling

vacuolar degeneration

inflammatory cell infiltration

and focal tubular necrosis. Compared with that in the model group

tubular damage in the BMAL1 overexpression+LPS group was reduced with only minimal inflammatory cell infiltration. (3) Relative expression levels of proteins KIM‑1

NGAL

Bax

p‑PI3K

PI3K

p‑Akt

and Akt in the model group were higher than those in the control group

while the expression levels of those proteins in the BMAL1 overexpression+LPS group were lower than those in the model group. The expression levels of kidney BMAL1 and Bcl‑2 proteins in model group were lower than those in the control group; however

the BMAL1 and Bcl‑2 proteins expression levels in the BMAL1 overexpression+LPS group were higher than those in the model group.

Conclusion

BMAL1 can downregulate the PI3K‑Akt pathway to inhibit cell apoptosis

thus playing a protective role in sepsis‑induced AKI. Overexpression of the BMAL1 gene can alleviate AKI caused by sepsis.

关键词

Keywords

references

POSTON J T , KOYNER J L . Sepsis associated acute kidney injury [J ] . BMJ (Clinical research ed) , 2019 , 364 : k4891 .

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 ( 6 ): 401 ‑ 417 .

PROWLE J R . Sepsis‑associated aki [J ] . Clin J Am Soc Nephrol , 2018 , 13 ( 2 ): 339 ‑ 342 .

RAY S , VALEKUNJA U K , STANGHERLIN A , et al . Circadian rhythms in the absence of the clock gene Bmal1 [J ] . Science , 2020 , 367 ( 6479 ): 800 ‑ 806 .

ZHENG Y , PAN L , WANG F , et al . Neural function of Bmal1: An overview [J ] . Cell Biosci , 2023 , 13 ( 1 ): 1 .

ZHANG B B , ZENG M N , LI B K , et al . Arbutin attenuates LPS‑induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway [J ] . Phytomedicine , 2021 , 82 : 153466 .

LIU C , CHEN K , WANG H , et al . Gastrin attenuates renal ischemia/reperfusion injury by a PI3K/Akt/bad‑mediated anti‑apoptosis signaling [J ] . Front Pharmacol , 2020 , 11 : 540479 .

SHEN Q , ZHANG X , LI Q , et al . TLR2 protects cisplatin‑induced acute kidney injury associated with autophagy via PI3K/Akt signaling pathway [J ] . J Cell Biochem , 2019 , 120 ( 3 ): 4366 ‑ 4374 .

XU H , ZHAO J , CHEN G , et al . Effects of BMAL1 on dentinogenic differentiation of dental pulp stem cells via PI3K/Akt/mTOR pathway [J ] . Int Endod J , 2022 , 55 ( 5 ): 505 ‑ 516 .

MANRIQUE‑CABALLERO C L , DEL RIO‑PERTUZ G , GOMEZ H . Sepsis‑associated acute kidney injury [J ] . Crit Care Clin , 2021 , 37 ( 2 ): 279 ‑ 301 .

CHEN W , ZHAO S , XING J , et al . BMAL1 inhibits renal fibrosis and renal interstitial inflammation by targeting the ERK1/2/ELK‑1/Egr‑1 axis [J ] . Int Immunopharmacol , 2023 , 125 ( Pt B ): 111140 .

LIN Q , LI S , JIANG N , et al . Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast‑induced acute kidney injury through the upregulation of HIF1A and BNIP3‑mediated mitophagy [J ] . Autophagy , 2021 , 17 ( 10 ): 2975 ‑ 2990 .

REN Q , GUO F , TAO S B , et al . Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src‑mediated NF‑κB p65 and MAPK signaling pathways in septic AKI mice [J ] . Biomed Pharmacother , 2020 , 122 : 109772 .

MAREMONTI F , MEYER C , LINKERMANN A . Mechanisms and models of kidney tubular necrosis and nephron loss [J ] . J Am Soc Nephrol , 2022 , 33 ( 3 ): 472 ‑ 486 .

LIN H , JI F , LIN K Q , et al . LPS‑aggravated ferroptosis via disrupting circadian rhythm by Bmal1/AKT/p53 in sepsis‑induced myocardial injury [J ] . Inflammation , 2023 , 46 ( 4 ): 1133 ‑ 1143 .

WANG Y T , XI W J , ZHANG X Y , et al . CTSB promotes sepsis‑induced acute kidney injury through activating mitochondrial apoptosis pathway [J ] . Front Immunol , 2023 , 13 : 1053754 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Tectorigenin alleviates doxorubicin‐induced cardiotoxicity through activating SIRT1/FOXO1 signaling pathway

Hesperetin alleviates high glucose and high lipid induced mitochondrial damage and apoptosis in AC16 cardiomyocytes via the AMPKα/SIRT1/PGC‐1α signaling pathway

Inhibiting UBE2O attenuates sepsis⁃induced acute lung injury by upregulating BMAL1 expression

Sodium 4‑phenylbutyrate alleviates H9c2 cell apoptosis induced by high glucose by inhibiting the endoplasmic reticulum stress‑MAMs‑mitochondrial calcium overload axis

Application effect of moxibustion combined with phototherapy in patients with diabetic foot

Related Author

YANG Songyuan

CHENG Fan

HU Xiaoli

LEI Ji

LI Jiahao

YUAN Xiaopin

XU Feixue

ZHANG Meng

Related Institution

Department of Cardiology, Gucheng Hospital Affiliated to Hubei University of Arts and Science, Xiangyang

Department of Cardiology, Second Hospital of Tianjin Medical University & Tianjin Key Laboratory of Ionic‐Molecular Function of Cardiovascular Disease

Department of Cardiology, Renmin Hospital of Wuhan University & Hubei Key Laboratory of Metabolic and Chronic Diseases

Department of Cardiology, Renmin Hospital of Wuhan University & Hubei Key Laboratory of Metabolic and Related Chronic Diseases

Department of Critical Care Medicine, Renmin Hospital of Wuhan University

AI问答

⁰