Department of Histology and Embryology, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China.
School of Nursing, Beijing University of Chinese Medicine, Beijing 102488, China.
World J Gastroenterol. 2020 Jun 7;26(21):2810-2820. doi: 10.3748/wjg.v26.i21.2810.
Liver fibrosis is a common health problem worldwide and there is still a lack of effective medicines. The Chinese herbal medicine, Gan Shen Fu Fang (GSFF) is composed of salvianolic acid B and diammonium glycyrrhizinate. In this study, we observed the effects of GSFF on liver fibrosis and in an attempt to provide some hope for the treatment.
To observe the effects of GSFF on liver fibrosis and and investigate the mechanism from the perspective of the inflammatory response and extracellular signal-regulated kinase (ERK) phosphorylation.
Common bile duct-ligated rats were used for experiments. Hepatic stellate cells-T6 (HSC-T6) cells were used for experiments. Hematoxylin and eosin staining and Masson staining, biochemical assays, hydroxyproline (Hyp) assays, enzyme-linked immunoasorbent assay and western blotting were performed to evaluate the degree of liver fibrosis, liver function, the inflammatory response and ERK phosphorylation. The CCK8 assay, immunofluorescence and western blotting were applied to test the effect of GSFF on HSC-T6 cell activation and determine whether GSFF had an effect on ERK phosphorylation in HSC-T6 cells.
GSFF improved liver function and inhibited liver fibrosis in common bile duct-ligated rats after 3 wk of treatment, as demonstrated by histological changes, hydroxyproline assays and collagen I concentrations. GSFF alleviated inflammatory cell infiltration and reduced the synthesis of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interlukin-1β] and NF-κB. In addition, GSFF decreased ERK phosphorylation. , GSFF inhibited the viability of HSC-T6 cells with and without transforming growth factor β1 (TGF-β1) stimulation and decreased the synthesis of collagen I. GSFF had the greatest effect at a concentration of 0.5 μmol/L. GSFF inhibited the expression of α-smooth muscle actin (α-SMA), a marker of HSC activation, in HSC-T6 cells. Consistent with the results, GSFF also inhibited the phosphorylation of ERK and downregulated the expression of NF-κB.
GSFF inhibited liver fibrosis progression and HSC-T6 cell activation . These effects may be related to an alleviated inflammatory response and downregulated ERK phosphorylation.
肝纤维化是一种常见的全球健康问题，目前仍缺乏有效的治疗药物。中药复方肝复方由丹参酚酸 B 和二铵甘草酸组成。本研究观察了肝复方对肝纤维化的作用，并试图从炎症反应和细胞外信号调节激酶（ERK）磷酸化的角度探讨其机制。
观察肝复方对肝纤维化的作用，并从炎症反应和 ERK 磷酸化的角度探讨其机制。
采用胆总管结扎大鼠进行实验。采用肝星状细胞-T6（HSC-T6）细胞进行实验。采用苏木精-伊红染色和 Masson 染色、生化测定、羟脯氨酸（Hyp）测定、酶联免疫吸附测定和 Western blot 测定评估肝纤维化程度、肝功能、炎症反应和 ERK 磷酸化。采用 CCK8 测定、免疫荧光和 Western blot 测定检测肝复方对 HSC-T6 细胞活化的影响，并确定肝复方是否对 HSC-T6 细胞的 ERK 磷酸化有影响。
肝复方治疗 3 周后改善胆总管结扎大鼠的肝功能，抑制肝纤维化，表现为组织学变化、羟脯氨酸测定和胶原 I 浓度降低。肝复方减轻炎症细胞浸润，减少促炎细胞因子[肿瘤坏死因子-α（TNF-α）和白细胞介素-1β]和 NF-κB 的合成。此外，肝复方降低 ERK 磷酸化。体外，肝复方抑制 TGF-β1 刺激和无刺激的 HSC-T6 细胞的活力，并减少胶原 I 的合成。在 0.5 μmol/L 浓度时效果最大。肝复方抑制 HSC-T6 细胞中α-平滑肌肌动蛋白（α-SMA）的表达，α-SMA 是 HSC 活化的标志物。与结果一致，肝复方还抑制 ERK 的磷酸化，并下调 NF-κB 的表达。
肝复方抑制肝纤维化进展和 HSC-T6 细胞活化。这些作用可能与炎症反应减轻和 ERK 磷酸化下调有关。
