The Kampo medicine "Daikenchuto (TU-100)" prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia.
The Kampo medicine "Daikenchuto (TU-100)" prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia.
复制标题
汉方药“大研中汤（TU-100）”可预防胆道闭锁大鼠模型中的细菌移位和肝纤维化。
DOI：
10.1016/j.surg.2016.02.002
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发表时间：
2016
期刊：
影响因子：
3.8
通讯作者：
Shimada M.
中科院分区：
文献类型：
--
作者：
Yada K;Ishibashi H;Mori H;Morine Y;Zhu C;Feng R;Kono T;Shimada M.
背景胆道闭锁是儿童终末期肝病最常见的病因。已知胆管结痂通过细菌易位（BT）和肝星状细胞（hsc）的toll样受体4 （TLR4）信号传导促进肝纤维化。我们以前曾报道过，传统的日本药物“大根拔”（TU-100），一种“汉布药”，可以防止暴露在禁食压力下的大鼠体内的BT。本研究的目的是阐明TU-100对胆管结扎大鼠胆道闭锁模型的影响。方法6周龄大鼠行胆管结扎术后每日口服TU-100。大鼠于胆管结扎后3、7、14天处死，观察肝损伤、BT发生及肝纤维化情况。作为体外实验，我们从胆管结扎大鼠中分离新鲜造血干细胞。细胞贴壁后，加入TU-100及其3种成分草药（如姜、人参、辣椒），分析α -肌动蛋白2 （acta2）、α -1型胶原蛋白（colIa1）、组织金属蛋白酶1 （timp1）的表达。结果体内实验表明，与仅行胆管结扎的大鼠相比，口服TU-100可减轻肝损伤、肠黏膜BT萎缩、肝纤维化、肝脏α -平滑肌肌动蛋白（αSMA）和TLR4的表达。体外实验表明，TU-100或其组份中药均能抑制hsc中acta2、colIa1和timp1的表达。结论tu -100对BT、hsc活化及肝纤维化具有抑制作用。TU-100可预防胆道闭锁患儿肝纤维化进展，改善预后。
BackgroundBiliary atresia is the most common cause of end-stage liver disease in children. It is known that bile duct ligation contributes to liver fibrosis via bacterial translocation (BT) and toll-like receptor 4 (TLR4) signaling of hepatic stellate cells (HSCs). We have reported previously that the traditional Japanese medicine, “Dai-kenchu-to (TU-100),” a form of “Kampo medicine” prevents BT in rats exposed to the stress of fasting. The aim of this study was to clarify the effect of TU-100 on a rat model of biliary atresia using bile duct ligation.MethodsBile duct ligation and subsequent daily oral administration of TU-100 was performed in 6-week-old rats. The rats were killed at 3, 7, or 14 days after bile duct ligation to evaluate the liver injury, occurrence of BT, and hepatic fibrosis. As an in vitro experiment, we isolated fresh HSCs from the rats undergoing bile duct ligation. After cell attachment, TU-100 and its 3 component herbs (eg, processed ginger, ginseng radix, and Japanese pepper) were added, and the expressions of Alpha actin2 (acta2), Alpha-1 type I collagen (colIa1), and tissue inhibitor of metalloproteinase 1 (timp1) were analyzed.ResultsIn vivo experiments demonstrated that oral administration of TU-100 decreased liver injury and atrophy of intestinal mucosa BT, hepatic fibrosis, and hepatic expression of alpha smooth muscle actin (αSMA) and TLR4, compared with rats that underwent bile duct ligation only. In vitro experiments showed that administration of TU-100 or the component herbs inhibited the expressions of acta2, colIa1, and timp1 in the HSCs.ConclusionTU-100 prevented BT, activation of HSCs, and subsequent hepatic fibrosis. TU-100 may prevent progression of hepatic fibrosis in children with biliary atresia and improve prognosis.