Ursolic acid enhances mouse liver regeneration after partial hepatectomy

Ursolic acid enhances mouse liver regeneration after partial hepatectomy
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DOI:
10.3109/13880209.2011.611143
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发表时间:
2012-04-01
影响因子:
3.8
通讯作者:
Jin, Nan-Ge
Jin, Nan-Ge
中科院分区:
医学3区
文献类型:
--
作者:
Jin, Yong-Ri;Jin, Jing-Ling;Jin, Nan-Ge

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背景:熊果酸是一种五环三萜类化合物,具有保肝和抗肝毒性活性。目的:本研究探讨熊果酸是否能够刺激部分肝切除小鼠的肝脏再生。材料与方法:实验组、假手术组和载体治疗组小鼠口服熊果酸或载体溶液7天,阳性对照动物(小鼠)给予重组人肝细胞生长因子(rhHGF)治疗,然后进行70%肝脏部分肝切除术。通过测量小鼠肝脏重量与体重的比率来估计肝脏质量恢复率。使用单克隆抗 BrdU 抗体通过免疫组织化学分析鉴定正在进行 DNA 合成的肝细胞。采用Western blotting技术检测cyclin D1、cyclin E和C/EBP蛋白(C/EBP α和C/EBP β)的表达水平。 结果:我们的结果显示,在部分肝切除术后36和48小时,给予熊果酸显着增加了肝脏与体重的比率和BrdU标记指数,并且UA的效力与rhHGF处理的阳性对照小鼠相似。此外,与媒介物处理的对照小鼠相比,熊果酸处理在肝PHx后36小时显着增加了cyclin D1、cyclin E和C/EBP beta蛋白表达水平。讨论和结论:所有这些结果表明熊果酸刺激部分肝切除术后的肝脏增殖,并且这种作用可能与刺激C/EBP beta表达有关。
Context: Ursolic acid is a pentacyclic triterpenoid which has hepatoprotective and antihepatotoxic activities. Objective: This study investigated whether ursolic acid is able to stimulate liver regeneration in partially hepatectomized mice.Materials and methods: Ursolic acid or the vehicle solution was orally administered to the experimental, sham-operated and vehicle-treated group mice for 7 days, positive control animal (mice) was treated with recombinant human hepatocyte growth factor (rhHGF), and then the 70% liver partial hepatectomy was performed. The liver mass recovery rate was estimated by measuring the ratios of mice liver weight to body weight. The liver cells undergoing DNA synthesis were identified by immunohistochemistry analysis using monoclonal anti-BrdU antibodies. The expression levels of cyclin D1, cyclin E and C/EBP proteins (C/EBP alpha and C/EBP beta) were detected by the Western blotting technique.Results: Our results showed administration of ursolic acid significantly increased the ratio of the liver to body weight and BrdU labeling index at 36 and 48 h after partial hepatectomy, and the potency of UA is similar to rhHGF treated positive control mice. In addition, ursolic acid treatment significantly increased cyclin D1, cyclin E and C/EBP beta protein expression levels at 36 h after liver PHx compared with the vehicle-treated control mice.Discussion and conclusion: All these results suggest that ursolic acid stimulates liver proliferation after partial hepatectomy, and this effect may be associated with the stimulation of C/EBP beta expression.