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Abstract：
The present study was designed to investigate the effects of betulinic acid on human hepatic stellate cells in vitro and C57BL/6 mice in vivo, as well as the signaling pathways involved. In this study, we explored the effects of betulinic acid on expression of alpha smooth muscle actin and autophagy-related proteins. Betulinic acid reduced pathological damage associated with liver fibrosis, as well as serum platelet-derived growth factor and serum hydroxyproline levels. Furthermore, betulinic acid downregulated the expression of alpha smooth muscle actin and type I collagen in mouse liver and upregulated the expression of microtubule-associated protein light chain 3B and autophagy-related gene 7 at the gene and protein levels. LC3II expression was increased and alpha smooth muscle actin expression was decreased in betulinic acid-treated hepatic stellate cells. Interventions with bafilomycin A1 and mCherry-GFP-LC3 adenoviruses promoted the formation of autophagosomes in hepatic stellate cells and the development of autophagic flow. Our study found that mitogen-activated protein kinase/extracellular signal-regulated kinase may be involved in the effects of betulinic acid on liver fibrosis. The present study suggests that betulinic acid has anti-hepatic fibrosis activity by inducing autophagy and could serve as a promising new agent for treating hepatic fibrosis.
摘要：
本研究旨在研究桦木酸对体外人肝星状细胞和体内C57BL/6小鼠的影响。以及所涉及的信号通路。在这项研究中,我们探讨了桦木酸对α平滑肌肌动蛋白和自噬相关蛋白表达的影响。桦木酸减少与肝纤维化相关的病理损伤，以及血清血小板源性生长因子和血清羟脯氨酸水平。此外，桦木酸下调小鼠肝脏中α平滑肌肌动蛋白和I型胶原蛋白的表达，并在基因和蛋白质水平上上调微管相关蛋白轻链3B和自噬相关基因7的表达。在桦木酸处理的肝星状细胞中，LC3II表达增加，α平滑肌肌动蛋白表达降低。bafilomycinA1和mCherry-GFP-LC3腺病毒的干预促进了肝星状细胞自噬体的形成和自噬流的发展。我们的研究发现丝裂原激活的蛋白激酶/细胞外信号调节激酶可能参与了桦木酸对肝纤维化的影响。本研究表明，桦木酸通过诱导自噬具有抗肝纤维化的活性，可作为一种有前途的治疗肝纤维化的新药。
