川芎嗪
自噬
肝星状细胞
肝纤维化
PI3K/AKT/mTOR通路
纤维化
炎症
癌症研究
蛋白激酶B
促炎细胞因子
药理学
医学
生物
免疫学
信号转导
病理
细胞凋亡
细胞生物学
生物化学
替代医学
作者
Zhigao Hu,Huizhao Su,Yonglian Zeng,Chengjie Lin,Zhenya Guo,Fudi Zhong,Keqing Jiang,Guandou Yuan,Songqing He
标识
DOI:10.1139/bcb-2019-0059
摘要
Background: Imbalanced immune response and hepatic fibrosis are key factors related to the progression of chronic liver diseases. Tetramethylpyrazine (TMP), a natural alkaloid, has been widely used for treating liver injury. In this study, we explored the effect of TMP on hepatic fibrosis and the related mechanisms regulating autophagy. Methods: A rat model of hepatic fibrosis and a model using an hepatic stellate cell line (HSC-T6) were created using CCl 4 and platelet-derived growth factor (PDGF). Staining with haematoxylin and eosin (HE), Masson’s stain, and TUNEL were performed for pathological diagnosis. ELISA, Western blotting, and immunofluorescence analyses were conducted to determine the expression levels of the specific markers for fibrosis, autophagy, inflammation, and signalling pathways. Results: TMP treatment significantly rescued pathological injury and hepatic fibrosis. It also alleviated imbalances in the immune system, accumulation of extracellular matrix, and autophagy signals in hepatic fibrosis. At the same time, we found that application of the autophagy inducer rapamycin enhanced the therapeutic effect of TMP, whereas the autophagy inhibitor 3-methyladenine, PI3K pathway inhibitor LY294002, and AKT pathway agonist SC79 did the opposite. Conclusions: TMP exerts therapeutic effects in hepatic fibrosis mainly through promoting autophagy to ameliorate inflammation by inhibiting the AKT–mTOR signalling pathway, providing a new perspective for the treatment of chronic liver diseases.
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