Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Lipids Health Dis. 2012 Mar 28;11:45. doi: 10.1186/1476-511X-11-45.
Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice.
C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs) and the expression of oxidative stress, inflammatory and fibrogenic related genes.
Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1) and Col-3.
Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.
扶正化瘀方(FZHY)是一种中药复方,据报道可改善乙型肝炎病毒感染患者的肝功能和纤维化。然而,其在营养性纤维性脂肪性肝炎中的作用尚不清楚。我们旨在阐明 FZHY 在小鼠这种疾病中的作用和分子机制。
C57BL/6 J 小鼠用蛋氨酸-胆碱缺乏(MCD)饮食喂养 8 周,诱导纤维性脂肪性肝炎。分别给予 FZHY 和/或血红素加氧酶-1(HO-1)化学诱导剂(血晶素)。通过比较肝损伤严重程度、肝脂质过氧化物水平、肝星状细胞(HSCs)活化和氧化应激、炎症和纤维化相关基因的表达,评估 FZHY 的作用。
用 MCD 饮食喂养 8 周的小鼠表现出严重的肝损伤,包括肝脂肪变性、坏死性炎症和纤维化。给予 FZHY 或血晶素可显著降低血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平,降低肝氧化应激,改善肝炎症和纤维化。在 MCD 补充 FZHY 或/和血晶素的小鼠中观察到相加作用。这些作用与下调促氧化应激基因细胞色素 P450 2E1、上调抗氧化基因血红素加氧酶-1有关;抑制促炎基因肿瘤坏死因子-α和白细胞介素-6;并抑制α-平滑肌肌动蛋白、转化生长因子-β1、I 型胶原(Col-1)和 Col-3 等促纤维化基因。
本研究表明 FZHY 具有改善营养性纤维性脂肪性肝炎的保护作用。这种作用是通过调节与氧化应激、炎症和纤维化相关的关键基因来介导的。