Network analysis and experimental verification of tanshinone ⅡA in treatment of autoimmune hepatitis

Jianheng HAO; Zhencheng LI; Weili SUN

doi:10.16016/j.2097-0927.202111049

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Network analysis and experimental verification of tanshinone ⅡA in treatment of autoimmune hepatitis

Basic Medicine | 更新时间：2026-01-09

- Network analysis and experimental verification of tanshinone ⅡA in treatment of autoimmune hepatitis
- Journal of Army Medical University Vol. 44, Issue 10, Pages: 1033-1040(2022)
- 作者机构：
  
  1.030619 山西晋中，山西中医药大学基础医学院中西医结合基础实验室
  2.030619 山西晋中，晋中市中医院风湿免疫科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202111049
  CLC： R318.04;R285.5;R575.1
- Received：07 November 2021，
  
  Revised：2022-01-09，
  
  Published：30 May 2022
- 稿件说明：
移动端阅览
Jianheng HAO, Zhencheng LI, Weili SUN. Network analysis and experimental verification of tanshinone ⅡA in treatment of autoimmune hepatitis[J]. Journal of Army Medical University, 2022, 44(10): 1033-1040.
DOI：

Jianheng HAO, Zhencheng LI, Weili SUN. Network analysis and experimental verification of tanshinone ⅡA in treatment of autoimmune hepatitis[J]. Journal of Army Medical University, 2022, 44(10): 1033-1040. DOI： 10.16016/j.2097-0927.202111049.

摘要

目的

基于网络药理学方法分析丹参酮ⅡA(tanshinoneⅡA，TanⅡA)治疗自身免疫性肝炎(autoimmune hepatitis，AIH)的潜在靶点与通路之间关系，并通过实验验证TanⅡA治疗AIH的作用机制。

方法

依托多个数据库检索筛选TanⅡA以及AIH的相关靶点基因，取药物和疾病的交集基因，借助String平台构建PPI网络，并对交集基因进行GO和KEGG通路富集分析。随后选择富集基因数最多信号通路通过动物实验进行验证，将小鼠按随机数字表法分为正常组、模型组和TanⅡA治疗组，每组6只；建模完成后检测各组小鼠血清谷丙转氨酶(alanine aminotransferase，ALT)、谷草转氨酶(aspartate aminotransferase，AST)的水平，并利用Western blot与qRT-PCR检测各组小鼠肝组织中PI3K、AKT和NF-κB蛋白及mRNA的表达。

结果

从TanⅡA中筛选得出有效作用靶点208个，收集到AIH的靶点基因7 128个。两者得到174个交集基因靶点。KEGG通路分析指出多条信号通路参与AIH的发病，其中PI3K-AKT信号通路可能在TanⅡA治疗AIH中起重要作用。动物实验结果显示，与正常组比较，模型组小鼠血清中ALT、AST水平均显著升高(

＜0.05)，肝组织中PI3K、AKT mRNA和蛋白表达均显著降低(

＜0.05)，NF-κB mRNA和蛋白表达均显著升高(

＜0.05)；与模型组比较，TanⅡA治疗组小鼠血清ALT、AST水平有不同程度减低(

＜0.05)，肝组织中PI3K、AKT mRNA和蛋白表达均显著升高(

＜0.05)，NF-κB mRNA水平和蛋白表达均显著降低(

＜0.05)。

结论

TanⅡA中包含许多可能直接靶向AIH相关信号通路的有效基因靶点，其中TanⅡA可能通过调节PI3K-AKT信号通路改善AIH小鼠肝脏炎症反应。

Abstract

Objective

To analyze the relationship between potential targets and signaling pathways of tanshinone Ⅱ A (Tan Ⅱ A) in the treatment of autoimmune hepatitis (AIH) based on network pharmacological analysis

and verify the mechanism of Tan Ⅱ A on AIH by animal experiments.

Methods

The relevant gene targets of Tan ⅡA and AIH were searched and screened through multiple databases

and the intersection genes between the drug and the disease were selected. Protein-protein interaction (PPI) network was subsequently constructed with the help of String platform

and the intersection genes were enriched and analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then

the signaling pathway with the highest number of enriched genes was verified through animal experiments. Eighteen C57BL/6 mice were equally and randomly divided into normal

model and Tan ⅡA treatment groups. The contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected

and the protein and mRNA expression levels of PI3K

AKT and NF-κB were measured by Western blotting and qRT-PCR respectively.

Results

There were 208 effective targets screened out from Tan ⅡA

and 7 128 target genes from AIH. A total of 174 intersection gene targets were obtained. KEGG pathway analysis indicated that multiple signaling pathways were involved in the pathogenesis of AIH

among which PI3K-AKT signaling pathway played an important role in Tan ⅡA treatment of AIH. In animal experiments

the model group had significantly higher contents of ALT and AST (

0.05)

reduced mRNA and protein levels of PI3K and AKT (

0.05) and elevated mRNA and protein levels of NF-κB (

0.05) than the control group. While

Tan ⅡA treatment resulted in decreased contents of ALT and AST (

0.05)

increased PI3K and AKT levels (

0.05) and decreased NF-κB level (

0.05) when compared with the model mice.

Conclusion

Tan ⅡA contains many effective genes that may directly target AIH-related signaling pathways

among which Tan ⅡA may ameliorate liver inflammation in AIH mice by regulating PI3K-AKT signaling pathway.

关键词

Keywords

references

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