咖啡酸苯乙酯抑制大鼠肝纤维化。
Caffeic acid phenethyl ester inhibits liver fibrosis in rats.
作者信息
Li Mei, Wang Xiu-Fang, Shi Juan-Juan, Li Ya-Ping, Yang Ning, Zhai Song, Dang Shuang-Suo
机构信息
Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
出版信息
World J Gastroenterol. 2015 Apr 7;21(13):3893-903. doi: 10.3748/wjg.v21.i13.3893.
AIM
To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis.
METHODS
A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n = 15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin (TBil), aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin (α-SMA), a characteristic hallmark of activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry.
RESULTS
Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats (P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group (P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group (P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group (P < 0.01).
CONCLUSION
The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.
目的
探讨咖啡酸苯乙酯（CAPE）对肝纤维化大鼠的肝保护作用及抗氧化活性。
方法
将75只雄性Sprague-Dawley大鼠随机分为7个实验组：正常组（n = 10）、溶剂对照组（n = 10）、模型组（n = 15）、维生素E组（n = 10）以及3个CAPE组（CAPE剂量分别为3、6和12 mg/kg，每组n = 10）。通过皮下注射四氯化碳、高脂饲料喂养及灌胃30%乙醇的方式诱导大鼠肝纤维化10周。同时，CAPE（3、6和12 mg/kg）每日腹腔注射给药10周。之后，检测血清总胆红素（TBil）、转氨酶（ALT）和天冬氨酸转氨酶（AST）水平以评估肝毒性。为研究CAPE的抗氧化活性，测定肝组织中丙二醛（MDA）、谷胱甘肽（GSH）水平以及过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性。此外，通过免疫组织化学法研究CAPE对α平滑肌肌动蛋白（α-SMA，活化肝星状细胞（HSCs）的特征性标志物）和NF-E2相关因子2（Nrf2，抗氧化系统的关键转录因子）的影响。
结果
与模型组相比，腹腔注射CAPE可降低肝纤维化大鼠的TBil、ALT和AST水平（P < 0.05），且血清TBil呈剂量依赖性降低。此外，6和12 mg/kg CAPE组的肝脏羟脯氨酸含量均显著低于模型组（分别为P < 0.05和P < 0.001）。与模型组相比，CAPE显著降低了肝纤维化大鼠的MDA水平，进而提高了GSH水平以及CAT和SOD活性（P < 0.05）。此外，与模型组相比，CAPE有效抑制了α-SMA表达，同时增加了Nrf2表达（P < 0.01）。
结论
CAPE对肝纤维化的保护作用可能归因于其通过抑制氧化应激来抑制肝星状细胞活化的能力。
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