Abstract：
Liver fibrosis is a wound-healing process. It can be induced by various chronic liver diseases. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs), a key event. However, no effective treatment strategies to cure or alleviate liver fibrosis-induced pathologic changes have yet been developed. Traditional Chinese medicine (TCM) exhibits a good anti-fibrosis action, with few side effects. Gentiana decoction, a TCM also called Longdan Xiegan Tang (LXT), is used for purging the liver in clinical settings. However, the role of LXT in preventing liver fibrosis and the underlying regulatory mechanism have not yet been investigated. This study demonstrates that LXT treatment can protect the liver from the injuries resulting from CCl4-induced liver fibrosis in mice and suppress the activation of HSCs. The mice in the LXT group exhibit litter collagen I and HSC activation marker α-smooth muscle actin (α-SMA) expression. Transcriptome sequencing of the mouse liver tissue reveals that the level of Parkin, a mitophagy marker, decreased in CCl4-induced liver fibrosis. Further study shows that the injection of Parkin-overexpression adeno-associated virus (Parkin-AAV) via the tail vein can reduce CCl4-induced liver fibrogenesis in mice. We conducted a mechanistic study also, which suggests that LXT treatment suppresses the activation of HSCs by upregulating the expression of Parkin. Hence, it can be suggested that LXT inhibits liver fibrosis by activating the Parkin signaling pathway.
摘要：
肝纤维化是一个伤口愈合过程。它可以由各种慢性肝病引起。肝纤维化的特征是肝星状细胞（HSC）的激活，一个关键事件。然而,尚未开发出治愈或减轻肝纤维化引起的病理变化的有效治疗策略。中药（TCM）具有良好的抗纤维化作用，副作用少。龙胆汤,一种中医也叫龙胆泻干汤(LXT)，用于在临床环境中清除肝脏。然而,LXT在预防肝纤维化中的作用和潜在的调节机制尚未被研究。这项研究表明，LXT治疗可以保护肝脏免受CCl4诱导的小鼠肝纤维化引起的损伤，并抑制HSC的活化。LXT组的小鼠表现出垫料胶原I和HSC激活标记α-平滑肌肌动蛋白（α-SMA）的表达。小鼠肝脏组织的转录组测序揭示了Parkin的水平，有丝分裂标记,减少CCl4诱导的肝纤维化。进一步的研究表明，经尾静脉注射Parkin过表达腺相关病毒（Parkin-AAV）可以减少小鼠CCl4诱导的肝纤维化发生。我们还进行了机械学研究，这表明LXT治疗通过上调Parkin的表达来抑制HSC的活化。因此，提示LXT通过激活Parkin信号通路抑制肝纤维化。
