A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation
A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation
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DOI：
10.1016/j.jep.2012.06.005
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发表时间：
2012-08-01
影响因子：
5.4
通讯作者：
Chen, Chuan-Mu
中科院分区：
文献类型：
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作者：
Chen, Jiun-Yu;Chen, Hsiao-Ling;Chen, Chuan-Mu
民族药理学证据：膈下逐瘀汤（GZT），又称膈下逐瘀汤（GXZYD），是一种治疗慢性肝病如肝硬化和肝纤维化的传统中药。本研究的目的：在本研究中，我们研究了GZT对二甲基亚硝胺（DMN）诱导的大鼠肝纤维化模型的影响。在这项研究中，GZT对DMN诱导的大鼠肝纤维化的保护作用进行了测量。在DMN治疗5周后（8 mg/kg，i. p.，每周连续给药3天），从第13周开始每天灌胃给予GZT 1.8g/kg，连续2周。体重和肝脏重量的降低与肝损伤严重程度的增加相对应。此外，GZT治疗显著降低DMN诱导的肝纤维化的血清GOT（谷草转氨酶）和GPT（谷丙转氨酶）水平，以及胶原α 1（1）和α-平滑肌肌动蛋白（α-SMA）mRNA表达水平。此外，肝星状细胞（HSC）通过初始肌成纤维细胞转化在各种类型的肝纤维化中发挥重要作用。GZT可抑制HSC的增殖。GZT处理还以剂量和时间依赖性方式诱导HSC凋亡。GZT处理6 h内通过促进线粒体Ca ~（2+）释放诱导HSC凋亡。随后，半胱天冬酶3和12升高72 h后treatment.Conclusions：我们的研究表明，GZT表现出肝保护和抗纤维化的DMN诱导的肝损伤的影响。这些结果表明，GZT可能有助于防止肝纤维化的发展。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological evidence: Gexia-Zhuyu Tang (GZT), also called Gexiazhuyu decoction (GXZYD), is a traditional Chinese herbal medicine for chronic liver diseases such as cirrhosis and liver fibrosis.Aim of the study: In this study, we have investigated the affects of GZT on a rat model of dimethylnitrosamine (DMN)-induced liver fibrosis.Materials and methods: In this study, the protective effects of GZT on DMN-induced liver fibrosis were measured using a rat model. Following 5 weeks of DMN-treatment (8 mg/kg, i.p., given 3 consecutive days each week), oral administration of GZT at 1.8 g/kg daily via oral gavage for 2 weeks beginning at week 13.Results: Both body and liver weights were significantly decreased. The reductions in body and liver weights corresponded with increasing liver damage severity. Furthermore, GZT-treatment remarkably decreased the levels of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase), and the mRNA expression levels of collagen alpha-1(1) and alpha-smooth muscle actin (alpha-SMA) in DMN-induced hepatic fibrosis. In addition, hepatic stellate cells (HSCs) play a major role in various types of liver fibrosis through initial myofibroblast transformation. The proliferation of HSCs was inhibited by GZT. Treatment with GZT also induced HSC apoptosis in a dose- and time-dependent manner. GZT treatment induced HSC apoptosis by facilitating Ca2+ release from the mitochondria within 6 h. Subsequently, caspases 3 and 12 were elevated by 72 h after treatment.Conclusions: Our studies indicate that GZT exhibited both hepatoprotective and antifibrogenic effects in DMN-induced hepatic injury. These findings suggest that GZT may be useful in preventing the development of hepatic fibrosis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.