Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice.
Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice.
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DOI：
10.1186/1476-511x-11-45
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发表时间：
2012-03-28
影响因子：
4.5
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Jia YH;Wang RQ;Mi HM;Kong LB;Ren WG;Li WC;Zhao SX;Zhang YG;Wu WJ;Nan YM;Yu J
扶正化瘀方（FZHY）是一种治疗B型肝炎病毒感染的中药复方。然而，其对营养性纤维化脂肪性肝炎的影响尚不清楚。本研究旨在阐明扶正化瘀方对小鼠肺纤维化的作用及其分子机制。C57 BL/6 J小鼠用蛋氨酸-胆碱缺乏（MCD）饲料喂养8周以诱导纤维化脂肪性肝炎。分别给予FZHY和/或血红素加氧酶-1（HO-1）化学诱导剂（氯化血红素）。通过比较肝损伤程度、肝脂质过氧化物水平、肝星状细胞（HSC）活化以及氧化应激、炎症和纤维化相关基因的表达来评估FZHY的作用。喂食MCD饲料8周的小鼠出现严重肝损伤，包括肝脂肪变性、坏死性炎症和纤维化。服用FZHY或氯化血红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，减轻肝脏氧化应激，改善肝脏炎症和纤维化。在喂食补充FZHY或/和氯化血红素的MCD的小鼠中观察到累加效应。这些作用与促氧化应激基因细胞色素P450 2 E1的下调、抗氧化基因HO-1的上调、促炎症基因肿瘤坏死因子α和白细胞介素-6的抑制以及促纤维化基因（包括α-平滑肌肌动蛋白、转化生长因子β 1、I型胶原（Col-1）和Col-3）的抑制有关。我们的研究表明FZHY在改善营养性纤维化脂肪性肝炎中的保护作用。该效应通过调节与氧化应激、炎症和纤维化相关的关键基因介导。
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.