Alpha-ketoglutarate alleviates cholestatic liver injury in mice

Yuhong XIE; Bo TANG; Chongxi FAN; Bairong LI; Tao SUN; Shoubin NING

doi:10.16016/j.2097-0927.202112271

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Alpha-ketoglutarate alleviates cholestatic liver injury in mice

Basic Medicine | 更新时间：2026-01-09

- Alpha-ketoglutarate alleviates cholestatic liver injury in mice
- Journal of Army Medical University Vol. 44, Issue 13, Pages: 1322-1329(2022)
- 作者机构：
  
  1.230032 合肥，安徽医科大学空军临床学院
  2.100142 北京，空军特色医学中心消化内科
  3.400037 重庆，陆军军医大学(第三军医大学)第二附属医院消化内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81873562);the Project of Air Force Medical Center of PLA(2021JX006)
- DOI：10.16016/j.2097-0927.202112271
  CLC： R575.05;R963;R977.4
- Received：30 December 2021，
  
  Revised：2022-03-16，
  
  Published：15 July 2022
- 稿件说明：
移动端阅览
Yuhong XIE, Bo TANG, Chongxi FAN, et al. Alpha-ketoglutarate alleviates cholestatic liver injury in mice[J]. Journal of Army Medical University, 2022, 44(13): 1322-1329.
DOI：

Yuhong XIE, Bo TANG, Chongxi FAN, et al. Alpha-ketoglutarate alleviates cholestatic liver injury in mice[J]. Journal of Army Medical University, 2022, 44(13): 1322-1329. DOI： 10.16016/j.2097-0927.202112271.

摘要

目的

探讨α-酮戊二酸(alpha-ketoglutarate，AKG)对小鼠胆管结扎(bile duct ligation，BDL)所致胆汁淤积性肝损伤的缓解作用及其机制。

方法

32只C57BL/6雄性小鼠按随机数字表法分为4组(每组8只): 假手术(Sham)组、假手术+AKG(Sham+AKG)组、胆管结扎(BDL)组、胆管结扎+AKG(BDL+AKG)组，所有小鼠均于术后7 d取材。检测血清ALT、AST、TBIL、TBA、ALP水平，HE染色评估各组肝组织损伤程度，免疫组化检测肝组织F4/80、MPO的表达水平，qRT-PCR检测肝组织促炎细胞因子mRNA表达水平，TUNEL染色观察肝细胞凋亡。

结果

与BDL组相比，BDL+AKG组小鼠血清ALT、AST、TBIL、TBA、ALP水平均明显降低(

0.05)，肝组织损伤程度明显减轻(

0.05)，F4/80、MPO表达减少(

0.05)，肝组织促炎细胞因子mRNA表达明显减少(

0.05)，TUNEL阳性肝细胞数目明显减少(

0.05)。

结论

α-酮戊二酸对小鼠胆管结扎所致胆汁淤积性肝损伤具有缓解作用，其机制可能与其抑制炎症反应和减少肝细胞凋亡有关。

Abstract

Objective

To investigate the alleviating effects of alpha-ketoglutarate (AKG) on bile duct ligation (BDL)-induced cholestatic liver injury in mice and its possible mechanism.

Methods

Thirty-two C57BL/6 male mice were randomly assigned to 4 groups (

=8): sham operation group (Sham)

sham operation+AKG group (Sham+AKG)

BDL group and BDL+AKG group. Liver and blood samples were collected from all groups in 7 d after operation

and the serum levels of ALT

AST

TBIL

TBA and ALP were measured. HE staining and immunohistochemistry were used to detect the severity of liver injury and the expression of F4/80 and myeloperoxidase (MPO) in each group

respectively. qRT-PCR was adopted to determine the mRNA expression of pro-inflammatory cytokines. Hepatocyte apoptosis was evaluated by TUNEL assay.

Results

As compared with the BDL group

the BDL+AKG group showed significantly lower concentrations of ALT

AST

TBIL

TBA and ALP (

0.05)

obviously relieved liver histologic injury (

0.05)

reduced expression levels of F4/80 and MPO as well as pro-inflammatory cytokines (

0.05)

and decreased number of TUNEL positive hepatocytes (

0.05).

Conclusion

AKG alleviates hepatic injury in BDL-induced cholestasis model mice

and its mechanism is possibly related to the inhibition of inflammatory response and hepatic cell apoptosis.

关键词

Keywords

references

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