Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung 435, Taiwan.
Biomed Pharmacother. 2024 May;174:116490. doi: 10.1016/j.biopha.2024.116490. Epub 2024 Mar 29.
Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF's protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF's mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF's ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1, as well as fibrogenic factors including α-Sma, Collagen I, and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis.
肝纤维化是一种由长期肝损伤引起的慢性肝病。细胞外基质的过度积累取代了受损的肝细胞，导致纤维性瘢痕形成和纤维化诱导。乳铁蛋白（LF）是一种具有保守的单体信号多肽链的糖蛋白，具有多种生理功能，包括抗氧化、抗炎、抗菌、抗真菌、抗病毒和抗肿瘤活性。先前的研究表明 LF 在大鼠化学诱导的肝纤维化中具有保护作用。然而，LF 在肝纤维化中的机制尚不清楚。在这项研究中，我们研究了 LF 在硫代乙酰胺（TAA）诱导的大鼠肝纤维化和 TGF-β1 处理的 HSC-T6 细胞中的作用机制。通过超声成像、H&E、Masson 和 Sirius Red 染色，我们证明了 LF 改善 TAA 诱导的肝组织损伤和纤维化的能力。LF 降低了 TAA 处理的肝组织中 ALT、AST 和羟脯氨酸的水平，同时增加了过氧化氢酶的水平。此外，LF 处理降低了 TAA 处理的肝组织中炎症因子如 Il-1β 和 Icam-1 以及纤维化因子如α-Sma、Collagen I 和 Ctgf 的 mRNA 表达。此外，LF 减少了 TAA 诱导的 FL83B 细胞中的 ROS 产生和细胞死亡，并减少了 TGF-β1 处理的 HSC-T6 细胞中 α-SMA、Collagen I 和 p-Smad2/3 的产生。我们的研究强调了 LF 改善 TAA 诱导的大鼠肝细胞损伤、氧化应激和肝纤维化的能力，可能是通过其对 HSC 激活的抑制作用。这些发现表明 LF 作为一种治疗剂具有保护肝脏免受损伤和纤维化的潜力。
