Effect of Sanhuang Yinchi Decoction in Preventing Acute Liver Injury by HMGB1 Signaling Pathway

Jia-yang WU; Jing-yu QUAN; Yan-xin ZHOU; Yi-meng CHEN; Jian-xin DIAO

doi:10.13422/j.cnki.syfjx.20190603

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Effect of Sanhuang Yinchi Decoction in Preventing Acute Liver Injury by HMGB1 Signaling Pathway

Pharmacology | 更新时间：2021-02-09

- Effect of Sanhuang Yinchi Decoction in Preventing Acute Liver Injury by HMGB1 Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 6, Pages: 58-64(2019)
- 作者机构：
  
  南方医科大学　中医药学院，广州　 510515
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190603
  CLC： R2-0;R22;R285.5;R289
- Received：22 August 2018，
  
  Published Online：12 May 2018，
  
  Published：20 March 2019
- 稿件说明：
移动端阅览
Jia-yang WU, Jing-yu QUAN, Yan-xin ZHOU, et al. Effect of Sanhuang Yinchi Decoction in Preventing Acute Liver Injury by HMGB1 Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(6): 58-64.
DOI：

Jia-yang WU, Jing-yu QUAN, Yan-xin ZHOU, et al. Effect of Sanhuang Yinchi Decoction in Preventing Acute Liver Injury by HMGB1 Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(6): 58-64. DOI： 10.13422/j.cnki.syfjx.20190603.

摘要

目的：

探究三黄茵赤汤通过调控高迁移率族蛋白B1(HMGB1)信号通路对四氯化碳(CCl

)致小鼠急性肝损伤的防治作用及机制。

方法：

随机将48只KM小鼠分为正常组，模型组，三黄茵赤汤低、中、高剂量组及促肝细胞生长素组，建立四氯化碳(CCl

)诱导小鼠急性肝损伤模型。三黄茵赤汤低、中、高剂量组分别以剂量为16，32，48 g·kg

－1

·d

－1

的药物灌胃，促肝细胞生长素组给予促肝细胞生长素20 mg·kg

－1

·d

－1

腹腔注射。小鼠肝组织切片病理学变化用苏木精-伊红(HE)染色观察；相关酶试剂盒测定小鼠血清中肝功能指标-丙氨酸氨基转移酶(AST)和天冬氨酸氨基转移酶(ALT)的活性；酶联免疫吸附测定(ELISA)测定小鼠血清中白细胞介素6(IL-6)的表达水平；蛋白免疫印迹法(Western blot)检测小鼠组织中HMGB1，天冬氨酸蛋白水解酶-3(Caspase-3)，凋亡相关分子B细胞淋巴瘤-2(Bcl-2)，Bcl-2相关x蛋白(Bax)和Toll样受体4(TLR4)的蛋白表达情况。

结果：

与正常组比较，模型组明显升高血清中AST，ALT(

0.05)和IL-6的水平(

0.05)以及增加肝组织中HMGB1，TLR4和Caspase-3表达(

0.05)并下调Bcl-2/Bax(

0.05)；与模型组比较，三黄茵赤汤各剂量组均能有效减轻小鼠肝脏的病理损害，降低血清中AST，ALT水平和降低IL-6的表达(

0.05)，不同程度降低降低肝组织匀浆中HMGB1，TLR4和Caspase-3蛋白的表达(

0.05)，并提高Bcl-2/Bax(

0.05)，呈剂量依赖性。

结论：

三黄茵赤汤可能通过调控HMGB1/TLR4/NF-

B信号通路，减轻细胞炎症反应，抑制细胞凋亡达到防治小鼠急性肝损伤的作用，HMGB1可能成为防治急性肝损伤的新靶点。

Abstract

Objective:

To investigate the effect and mechanism of Sanhuang Yinchi decoction (SHYCD) in preventing carbon tetrachloride (CCl

)-induced acute liver injury by regulating high mobility group box1(HMGB1) signaling pathway.

Method:

A total of 48 KM mice were randomly divided into blank control group

model group

low

middle and high-dose SHYCD groups and positive control group. The model of acute liver injury induced by CCl

in mice was established. The low

middle and high-dose SHYCD groups were intragastrically administered with drugs (16

48 g·kg

-1

·d

-1

) respectively

and the positive control group was given cell growth stimulating hormone (20 mg·kg

-1

·d

-1

) through intraperitoneal injection. Pathological changes of mouse liver tissue sections were observed by hematoxylin-eosin staining (HE); relevant enzyme kits were used to determine liver function indexes in mice serum-alanine aminotransferase (AST) and aspartate aminotransferase (ALT); the expression level of interleukin-6 (IL-6) in mouse serum was determined by enzyme-linked immunosorbent assay (ELISA); Western blot was used to detect the expressions of high mobility group box-1(HMGB1)

cysteine aspartic acid protease(Caspase-3)

apoptosis-related molecules B cell lymphoma(Bcl-2)

Bcl-2 associated x protein(Bax)

and Toll-like receptor 4 (TLR4).

Result:

Compared with the normal group

the model group significantly increased serum AST

ALT (

0.05) and IL-6 levels (

0.05) and expressions of HMGB1

TLR4 and Caspase-3 (P

0.05)

and down-regulated Bcl-2/Bax ratio (

0.05) in liver tissue; compared with the model group

SHYCD can effectively alleviate the pathological damage of liver in mice

reduce serum AST and ALT levels and expressions of IL-6

HMGB1

TLR4 and Caspase-3 protein in liver homogenate (

0.05)

and increased the ratio of Bcl-2/Bax (

0.05) in a dose-dependent manner.

Conclusion:

SHYCD can prevent liver injury by regulating HMGB1/TLR4/NF-

B signaling pathway

reducing cellular inflammatory response and inhibiting apoptosis

so as to prevent acute liver injury in mice. This indicates that HMGB1 may become a new target to prevent acute liver injury.

关键词

Keywords

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