Guangxi Medical University, Nanning 530021, China.
J Ethnopharmacol. 2012 Jul 13;142(2):548-56. doi: 10.1016/j.jep.2012.05.040. Epub 2012 May 31.
Chinese prescription Fufang-Liu-Yue-Qing (FLYQ) has long been employed clinically to treat chronic hepatitis B, and we have reported its beneficial effects on liver fibrosis in vitro. The present study was investigated to verify protective effects of FLYQ on liver fibrosis in a rat model and to investigate the underlying mechanisms which have not been explored yet.
Liver fibrosis was established by intragastric administration of 2 ml/kg CCl(4) twice a week for 12 weeks. During the experiment, the model group received CCl(4) only, and the normal control group received an equal volume of saline. Treatment groups received not only CCl(4) for 12 weeks, but also the corresponding drugs, colchicine (1.00 mg/kg/day) or FLYQ (300, 150, 75 mg/kg/day) from 5 to 12 weeks.
Analysis experiments showed that FLYQ could significantly alleviate liver injury, as indicated by decreasing levels of ALT, AST, ALP, GGT, IL-6 and TNF-α. Moreover, FLYQ could effectively inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that FLYQ was able to markedly reduce lipid peroxidation, recruit the anti-oxidative defense system, promote ECM degradation by modulating the levels of TIMP-1 and MMP-2, and induce HSC apoptosis by down-regulating bcl-2 mRNA, as well as inhibit the expressions of α-SMA and TGF-β(1) proteins.
Our results show that FLYQ is effective in attenuating hepatic injury and fibrosis in the CCl(4)-induced rat model, which should be developed as a new drug for treatment of liver fibrosis and even cirrhosis.
中药复方六药清肝方(FLYQ)长期以来一直被临床用于治疗慢性乙型肝炎,我们已经报道了其在体外抗肝纤维化的有益作用。本研究旨在验证 FLYQ 在大鼠肝纤维化模型中的保护作用,并探讨尚未探索的潜在机制。
通过每周两次胃内给予 2ml/kg CCl4 建立肝纤维化模型,共 12 周。实验期间,模型组仅给予 CCl4,正常对照组给予等体积生理盐水。治疗组不仅在 12 周内给予 CCl4,还在第 5-12 周给予相应的药物秋水仙碱(1.00mg/kg/天)或 FLYQ(300、150、75mg/kg/天)。
分析实验表明,FLYQ 可显著减轻肝损伤,表现为 ALT、AST、ALP、GGT、IL-6 和 TNF-α 水平降低。此外,FLYQ 能有效抑制胶原沉积,减轻病理组织损伤。机制研究表明,FLYQ 能显著降低脂质过氧化,募集抗氧化防御系统,通过调节 TIMP-1 和 MMP-2 水平促进 ECM 降解,并通过下调 bcl-2mRNA 诱导 HSC 凋亡,同时抑制 α-SMA 和 TGF-β1 蛋白的表达。
我们的结果表明,FLYQ 能有效减轻 CCl4 诱导的大鼠肝损伤和纤维化,可开发为治疗肝纤维化甚至肝硬化的新药。