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三黄柴术方通过抑制SIRT1/PGC-1调节的线粒体氧化应激改善肝内胆汁淤积中的肝损伤。

San-Huang-Chai-Zhu Formula Ameliorates Liver Injury in Intrahepatic Cholestasis through Suppressing SIRT1/PGC-1-Regulated Mitochondrial Oxidative Stress.

作者信息

Liu Binbin, Zhang Jie, Shao Lu, Yao Jiaming

机构信息

Department of Digestion, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, China.

出版信息

Evid Based Complement Alternat Med. 2022 Jul 8;2022:7832540. doi: 10.1155/2022/7832540. eCollection 2022.

DOI:10.1155/2022/7832540
PMID:35845569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9286970/
Abstract

BACKGROUND

Chinese herbal formulae possess promising applications in treating intrahepatic cholestasis.

OBJECTIVE

Our study aims to explore the protective effect of the San-Huang-Chai-Zhu formula (SHCZF) on liver injury in intrahepatic cholestasis (IC) and investigate the underlying mechanism related to mitochondrial oxidative stress.

METHODS

An IC rat model was established by -naphthyl isothiocyanate induction. Hepatic histomorphology was observed through hematoxylin and eosin staining. Levels of biochemical indexes of hepatic function and oxidative stress were determined by an enzyme-linked immunosorbent assay. Cell apoptosis in liver tissues was detected by the TUNEL assay. The mRNA expression of mtDNA, SIRT1, and PGC-1 was measured by qRT-PCR, and the protein expression of Bax, Bcl-2, caspase-3, SIRT1, and PGC-1 was determined by Western blotting.

RESULTS

SHCZF treatment attenuated liver injury in IC. Levels of hepatic function parameters were decreased after SHCZF administration. In addition, the decreased level of malondialdehyde (MDA) and the increased levels of superoxide dismutase (SOD), glutathione (GSH), and adenosine triphosphate (ATP) in hepatic mitochondria confirmed that SHCZF could attenuate oxidative stress in IC. SHCZF treatment also reduced the apoptosis in the liver tissues of IC rats. Furthermore, SHCZF administration upregulated the expression of mtDNA, SIRT1, and PGC-1 in IC.

CONCLUSIONS

SHCZF exerts a protective effect on liver injury in IC via alleviating SIRT1/PGC-1-regulated mitochondrial oxidative stress.

摘要

背景

中药方剂在治疗肝内胆汁淤积方面具有广阔的应用前景。

目的

本研究旨在探讨三黄柴术方（SHCZF）对肝内胆汁淤积（IC）肝损伤的保护作用，并研究其与线粒体氧化应激相关的潜在机制。

方法

通过异硫氰酸 -萘酯诱导建立IC大鼠模型。通过苏木精 -伊红染色观察肝脏组织形态学。采用酶联免疫吸附测定法测定肝功能和氧化应激的生化指标水平。采用TUNEL法检测肝组织中的细胞凋亡。通过qRT-PCR检测mtDNA、SIRT1和PGC-1的mRNA表达，并通过蛋白质印迹法测定Bax、Bcl-2、caspase-3、SIRT1和PGC-1的蛋白质表达。

结果

SHCZF治疗减轻了IC中的肝损伤。给予SHCZF后肝功能参数水平降低。此外，肝线粒体中丙二醛（MDA）水平降低，超氧化物歧化酶（SOD）、谷胱甘肽（GSH）和三磷酸腺苷（ATP）水平升高，证实SHCZF可减轻IC中的氧化应激。SHCZF治疗还减少了IC大鼠肝组织中的细胞凋亡。此外，给予SHCZF上调了IC中mtDNA、SIRT1和PGC-1的表达。

结论

SHCZF通过减轻SIRT1/PGC-1调节的线粒体氧化应激对IC肝损伤发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/b1c8baacebfb/ECAM2022-7832540.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/0e1a7918e313/ECAM2022-7832540.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/1fe455075b1c/ECAM2022-7832540.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/fe2842c0ab09/ECAM2022-7832540.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/776b43308c31/ECAM2022-7832540.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/6e39e0c7aaf9/ECAM2022-7832540.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/b1c8baacebfb/ECAM2022-7832540.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/0e1a7918e313/ECAM2022-7832540.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/1fe455075b1c/ECAM2022-7832540.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/fe2842c0ab09/ECAM2022-7832540.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/776b43308c31/ECAM2022-7832540.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/6e39e0c7aaf9/ECAM2022-7832540.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a2/9286970/b1c8baacebfb/ECAM2022-7832540.006.jpg

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