Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China.
Department of Infectious Diseases, The First Affiliated Hospital of Jiaxing College, Jiaxing 314000, People's Republic of China.
Drug Des Devel Ther. 2020 Mar 31;14:1295-1305. doi: 10.2147/DDDT.S233665. eCollection 2020.
Liver fibrosis (or liver scarring) is a causative factor for hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Alginate (Agn) isolated from brown algae is known to slow the proliferation of fibroblasts, through the mechanisms of these effects remain undefined. This study explored the benefits of Agn on hepatic health and its associated mechanism(s) of action in hepatic stellate cells (HSC-T6s).
To assess the effects of Agn, HSC-T6s were treated with PDGF and cell proliferation, colony formation, cell migration, cell invasiveness and apoptosis were assessed. Rat models of liver fibrosis were produced through 12-week injections of intraperitoneal (IP) carbon tetrachloride (CCl). Rats were Agn-treated from weeks 8 to 12, and liver damage was assessed through Masson's and H & E staining. Gene expression profiles were assayed via RT-PCR, Western blot and commercial ELISA kits.
Agn reduced the proliferation of HSC-T6s and increased apoptotic rates through the downregulation of the Bcl-2:Bax ratio. Agn also inhibited the invasion and migration of HSC-T6s, prevented ECM deposition, and reduced the occurrence of liver fibrosis in rat models. Agn also prevented IκBα and p65 phosphorylation.
Agn prevents liver fibrosis through its attenuation of HSC activation and division through the suppression of NF-κB in in vitro and animal models. This highlights how the clinical use of Agn can prevent hepatic fibrosis.
肝纤维化（或肝瘢痕）是肝炎、肝硬化和肝细胞癌（HCC）的致病因素。从褐藻中分离出的褐藻酸钠（Agn）已知可通过这些作用的机制减缓成纤维细胞的增殖，但这些作用的机制仍未确定。本研究探讨了褐藻酸钠对肝健康的益处及其在肝星状细胞（HSC-T6）中的作用机制。
为了评估 Agn 的作用，用 PDGF 处理 HSC-T6，评估细胞增殖、集落形成、细胞迁移、细胞侵袭和细胞凋亡。通过腹腔内（IP）四氯化碳（CCl）注射，在大鼠中产生肝纤维化模型。从第 8 周到第 12 周，大鼠用 Agn 治疗，通过 Masson 和 H & E 染色评估肝损伤。通过 RT-PCR、Western blot 和商业 ELISA 试剂盒检测基因表达谱。
褐藻酸钠通过下调 Bcl-2:Bax 比值，减少 HSC-T6 的增殖并增加细胞凋亡率。褐藻酸钠还抑制 HSC-T6 的侵袭和迁移，防止 ECM 沉积，并减少大鼠模型中肝纤维化的发生。褐藻酸钠还防止了 IκBα 和 p65 的磷酸化。
褐藻酸钠通过抑制 NF-κB 在体外和动物模型中抑制 HSC 的激活和分裂，防止肝纤维化。这突出了临床应用褐藻酸钠预防肝纤维化的可能性。
