The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease.
The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease.
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DOI：
10.1016/j.jep.2016.01.030
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发表时间：
2016-03
影响因子：
5.4
通讯作者：
Shengyan Xi;M. Shi;Xueqiang Jiang;G. Minuk;Yao Cheng;Ying Peng;Y. Gong;Y. Xu;Xinrong Wang;Jiaqi Yang;Li-feng Yue;Yanhui Wang
中科院分区：
文献类型：
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作者：
Shengyan Xi;M. Shi;Xueqiang Jiang;G. Minuk;Yao Cheng;Ying Peng;Y. Gong;Y. Xu;Xinrong Wang;Jiaqi Yang;Li-feng Yue;Yanhui Wang
桃红四物汤(THSWD)是一种用于治疗慢性肝病的中草药，已有数百年的历史。近年来，有报道THSWD改变血管内皮生长因子(VEGF)诱导的血管生成，增加了THSWD除具有抗炎作用外，还可抑制肝血流相关性纤维化的可能性。目的探讨THSWD对慢性肝病小鼠肝脏坏死炎性疾病活动、纤维化及血管内皮生长因子信号转导的影响。5组动物皮下注射四氯化碳(0.1g/10g体重)，连续6周。其中3组给予不同浓度的THSWD(4.25、8.50、17.00 mg/kg)，1组给予秋水仙碱0.1 mg/kg(阳性对照)，1组给予生理盐水(阴性对照)。第六组小鼠没有接触CCl4，仍然没有接受治疗(健康对照组)。治疗结束时检测肝酶/功能试验、血清透明质酸和层粘连蛋白水平，并观察肝组织学改变、肝组织血管内皮生长因子、Flt-1和蛋白激酶插入结构域受体(KDR)、Akt和磷酸化Akt(PACT)的表达。这些有益的结果是相似的，而且经常超过秋水仙素的效果。此外，TSHWD治疗组小鼠肝组织中VEGF、Flt-1、KDR、Akt和Pakt的mRNA和蛋白表达均降低。结论在慢性肝病动物模型中，THSWD可减轻肝组织坏死性炎症和肝纤维化。抑制血管内皮生长因子的表达和下游信号转导与这些发现有关。该中药和其他中药治疗慢性肝病的进一步研究是有必要的。
BackgroundTao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine that has been used for centuries in the treatment of Chinese patients with chronic liver disease. Recently, THSWD has been reported to alter vascular endothelial growth factor (VEGF) induced angiogenesis, raising the possibility that in addition to its anti-inflammatory properties; THSWD might also inhibit hepatic blood flow associated fibrosis.AimTo document the effects of THSWD on hepatic necroinflammatory disease activity, fibrosis and VEGF signaling in a murine model of chronic liver disease.MethodsSixty adult mice were equally divided into six study groups. Five groups were exposed to subcutaneous carbon tetrachloride (0.1 ml/10 g BW) for six weeks. Three of the five groups were treated with different concentrations of THSWD (4.25, 8.50, 17.00 g/kg), one with 0.1 mg/kg of Colchicine (positive control), and one with physiologic saline (negative control). Mice in the sixth group were not exposed to CCl4and remained untreated (healthy controls). Liver enzymes/function tests, hyaluronic acid and laminin levels were measured in serum, and hepatic histology, VEGF, Flt-1 and kinase insert domain-containing receptor (KDR), Akt and phosphorylated Akt (pAkt) expression were documented in liver tissue at the end of treatment.ResultsHepatic necroinflammatory disease activity and fibrosis were significantly attenuated in THSWD treated mice in a dose dependent manner. These beneficial results were similar and often exceeded those achieved with Colchicine. In addition, VEGF, Flt-1, KDR, Akt and pAkt mRNA and protein expression were reduced in TSHWD treated mice.ConclusionsIn this animal model of chronic liver disease, THSWD decreased hepatic necroinflammatory disease and fibrosis. Inhibition of VEGF expression and downstream signaling were associated with these findings. Further studies with this and other TCMs as treatment for chronic liver disease are warranted.