Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury

Ping-sheng ZHU; Yan-jie JIAO; Shuang-nan FU; Ming-san MIAO; Yu MENG; Zheng-wang ZHU; Da GAO

doi:10.13422/j.cnki.syfjx.20190221

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Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury

Topic on Changes of Biomarkers in Animal Models of Early Liver Injury | 更新时间：2021-02-09

- Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 2, Pages: 118-123(2019)
- 作者机构：
  
  河南中医药大学，郑州　 450046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190221
  CLC： R2-0; R22; R285.5
- Received：21 July 2018，
  
  Published Online：26 October 2018，
  
  Published：20 January 2019
- 稿件说明：
移动端阅览
Ping-sheng ZHU, Yan-jie JIAO, Shuang-nan FU, et al. Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 118-123.
DOI：

Ping-sheng ZHU, Yan-jie JIAO, Shuang-nan FU, et al. Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 118-123. DOI： 10.13422/j.cnki.syfjx.20190221.

摘要

目的：

通过比较对乙酰氨基酚(APAP)致肝损伤模型大鼠传统生物标志物丙氨酸氨基转移酶(ALT)，天冬氨酸氨基转移酶(AST)，碱性磷酸酶(ALP)，总胆红素(TBIL)和潜在生物标志物谷氨酸脱氢酶(GLDH)，嘌呤核苷酸磷酸化酶(PNP)，

-谷胱甘肽-

-转移酶(

-GST)，精氨酸酶1(Arg1)的变化来判断GLDH，PNP，

-GST，Arg1是否可以作为检测药物性肝损伤的早期生物标志物。

方法：

48只大鼠随机分为2组，分为正常组、模型组，每组24只，雌雄各半。给予模型组灌胃1 250 mg·kg

－1

APAP溶液复制药物性肝损伤的模型，在给予APAP后3，6，12，24 h，每个时间点每组随机取6只大鼠(雌雄各半)，检测血清ALT，AST，ALP，TBIL，GLDH，PNP，

-GST，Arg1水平及肝组织匀浆GLDH，PNP，

-GST，Arg1水平；苏木素-伊红(HE)染色检查肝组织病理学变化。

结果：

与正常组比较，模型组大鼠血清和肝组织匀浆的ALT，AST，ALP，TBIL，GLDH，PNP，

-GST，Arg1水平均明显升高(

0.05，

0.01)，表明APAP致药物性肝损伤模型复制成功。模型组大鼠血清和肝组织的GLDH，PNP，

-GST，Arg1水平比ALT，AST水平升高时间早，幅度大。

结论：

GLDH，PNP，

-GST，Arg1较传统肝功能检测指标具有较好的灵敏性，可以作为早期检测药物性肝损伤的生物标志物。

Abstract

Objective:

To determine whether glutathione dehydrogenase (GLDH)

purine nucleotide phosphorylase (PNP)

-glutathione-

-transferase (

-GST)

and arginase 1 (Arg1) can be used as the early biomarkers of drug-induced liver injury by comparing the changes of traditional biomarkers alanine aminotransferase (ALT)

aspartate aminotransferase (AST) and alkaline phosphatase (ALP)

total bilirubin (TBIL) and potential biomarkers GLDH

PNP

-GST and Arg1 in acetaminophen (APAP)-induced liver injury model rats.

Method:

The 48 rats were randomly divided into two groups: blank group and model group. 24 rats in each group

half male and half female. The model group received 1 250 mg·kg

-1

APAP solution by intragastric administration to establish the drug-induced liver injury. 6 rats (half male and half female) were randomly selected from each group at 3

12 and 24 h after APAP was given to the model group

to detect the levels of ALT

AST

ALP

TBIL

GLDH

PNP

-GST

Arg1 in serum and levels of GLDH

PNP

-GST

Arg1 in liver tissue homogenate at each time point Histopathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining.

Result:

As compared with the blank group

the levels of ALT

AST

ALP

TBIL

GLDH

PNP

-GST and Arg1 in serum and liver homogenates were significantly increased in model group(

0.05

0.01)

indicating that the APAP-induced liver injury model was successfully replicated. GLDH

PNP

-GST and Arg1 levels in serum and liver tissues of rats in the model group were increased earlier and more significantly than ALT and AST levels.

Conclusion:

GLDH

PNP

-GST and Arg1 can be used as biomarkers for early detection of drug-induced liver injury.

关键词

Keywords

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