Clinical Research Center, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, China; Department of General Surgery, Chengdu Qingbaijiang District People's Hospital, Chengdu, China.
Bioorg Chem. 2022 Sep;126:105899. doi: 10.1016/j.bioorg.2022.105899. Epub 2022 May 25.
Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl-l-tryptophan (l-NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l-NAT on liver fibrosis is not determined.
The present study investigated the effect of l-NAT on liver fibrosis and explored it potential molecular mechanism.
To address this concern, this study was carried out via fibrotic mice model induced by CCl and many approaches such as various histological staining methods, western blot assay, etc. RESULT: l-NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl). Histological staining showed that l-NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l-NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l-NAT inhibited the expressions of TGF-β1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl-induced liver fibrosis.
These results clearly demonstrated that l-NAT attenuated CCl-induced liver fibrosis in mice, and this protective mechanism might relate to TGF-β1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.
尽管肝纤维化是许多肝脏疾病的关键病理过程，但抑制肝纤维化的治疗方法仍然非常有限。N-乙酰-L-色氨酸（l-NAT）通过抑制肝细胞破坏、增强细胞活力和减少炎症具有保肝作用。然而，l-NAT 对肝纤维化的影响尚不确定。
本研究探讨了 l-NAT 对肝纤维化的影响，并探讨了其潜在的分子机制。
为了解决这个问题，本研究通过 CCl 诱导的纤维化小鼠模型以及各种组织学染色方法、Western blot 检测等方法进行了研究。
l-NAT 降低了四氯化碳（CCl）诱导的纤维化小鼠模型中丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平。组织学染色显示，l-NAT 改善了肝损伤和纤维化，并降低了α-平滑肌肌动蛋白（α-SMA）和胶原 I 蛋白的表达。l-NAT 通过下调促凋亡蛋白 Bax 的水平和上调抗凋亡蛋白 Bcl-2 的水平，还减轻了细胞凋亡。此外，l-NAT 抑制了 TGF-β1/SMAD 和基质金属蛋白酶 9（MMP9）蛋白的表达，并逆转了 CCl 诱导的肝纤维化中 YAP1 蛋白的表达。
这些结果清楚地表明，l-NAT 减轻了 CCl 诱导的小鼠肝纤维化，这种保护机制可能与 TGF-β1/SMAD 和 Hippo/YAP1 信号通路有关。因此，本研究为肝纤维化的防治提供了数据基础。
