Xiong Yu, Hu Jinyuan, Xuan Chen, Tian Jiayu, Tan Kaiyue, Chen Zhiwei, Luo Yan, Du Xuqin, Cheng Junxiong, Zhang Lanyue, Cao Wenfu
College of Traditional Chinese Medicine, Chongqing Medical University, No. 1 Medical College Road, Yuzhong District, Chongqing, 400016, China.
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, 400016, China.
Chin Med. 2021 Dec 24;16(1):142. doi: 10.1186/s13020-021-00552-w.
Liver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl)-induced liver fibrosis in rats and its molecular mechanism.
We used low-, medium-, and high-dose YQRG to treat CCl-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot and real-time quantitative PCR.
The results showed that YQRG effectively alleviated CCl-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these findings subsequently verified experimentally.
These findings showed that YQRG improved CCl-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.
肝纤维化由多种慢性肝病发展而来，目前缺乏特异性治疗策略。益气柔肝汤（YQRG）是一种传统中药，已显示出对肝纤维化的持续治疗效果；然而，YQRG改善肝纤维化的相关机制仍有待通过实验确定。本研究评估了YQRG对四氯化碳（CCl）诱导的大鼠肝纤维化的治疗效果及其分子机制。
我们使用低、中、高剂量的YQRG治疗CCl诱导的大鼠肝纤维化，然后根据肝脏外观、体重、肝脏质量指数、组织病理学检查和血清检测评估肝损伤和纤维化情况。此外，我们使用RNA测序（RNA-seq）技术进行转录组分析，包括聚类、基因本体（GO）和通路分析，以鉴定差异表达基因（DEG），并通过免疫荧光（IFC）、蛋白质印迹和实时定量PCR检测蛋白质和基因表达。
结果表明，YQRG有效减轻了CCl诱导的大鼠肝损伤和纤维化，包括肝功能改善、肝星状细胞（HSC）活性降低和细胞外基质（ECM）沉积减少。此外，我们鉴定出模型组相对于对照组和YQRG治疗组的下调和上调DEG，GO分析显示它们在生物过程中富集，如内质网应激（ERS）、细胞凋亡和自噬。此外，通路分析表明，YQRG治疗下调了丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）信号通路，并上调了其他信号通路，包括与过氧化物酶体增殖物激活受体（PPAR）和AMP激活的蛋白激酶（AMPK）相关的信号通路，这些发现随后通过实验得到验证。
这些发现表明，YQRG通过多种机制和途径改善CCl诱导的肝纤维化，为YQRG相关的治疗机制提供了关键见解，并促进了对其潜在应用的进一步研究。
