Li Jian-ping, Gao Yan, Chu Shi-feng, Zhang Zhao, Xia Cong-yuan, Mou Zheng, Song Xiu-yun, He Wen-bin, Guo Xiao-feng, Chen Nai-hong
State Key of Laboratory Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
1] State Key of Laboratory Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China [2] Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China.
Acta Pharmacol Sin. 2014 Aug;35(8):1031-44. doi: 10.1038/aps.2014.41. Epub 2014 Jun 30.
To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects.
Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies.
In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro.
Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes.
研究人参皂苷Rg1对酒精和四氯化碳诱导的大鼠肝纤维化的抗纤维化作用，并探讨其作用机制。
大鼠饮用含6%酒精的水，并每周两次皮下注射四氯化碳（2 mL/kg），持续8周。在最后2周给予Rg1（每天10、20和40 mg/kg，口服）。通过检测血清生化参数、HE染色、Masson三色染色以及肝组织中羟脯氨酸和α-SMA免疫组化染色来确定肝纤维化情况。分析肝组织中抗氧化酶活性、脂质过氧化以及Nrf2信号通路相关蛋白（Nrf2、Ho-1和Nqo1）。制备大鼠培养的肝星状细胞（HSCs）用于体外研究。
在酒精和四氯化碳处理的大鼠中，给予Rg1剂量依赖性地抑制了血清ALT、AST、LDH和ALP水平的显著升高，抑制了肝脏炎症和肝星状细胞活化，并降低了肝纤维化评分。Rg1显著提高了肝组织中抗氧化酶（SOD、GSH-Px和CAT）的活性，并降低了MDA水平。此外，Rg1显著增加了调节多种抗氧化酶表达的Nrf2的表达和核转位。用Rg1（1 μmol/L）处理培养的肝星状细胞可诱导Nrf2转位，并抑制四氯化碳诱导的细胞增殖，逆转四氯化碳诱导的上清液中MDA、GPX、PCIII和HA含量的变化以及细胞中α-SMA的表达。敲低Nrf2基因可减弱Rg1在体外对四氯化碳处理的肝星状细胞的这些作用。
Rg1通过促进Nrf2的核转位和抗氧化酶的表达，对酒精和四氯化碳诱导的大鼠肝纤维化模型发挥保护作用。
