Huang Qi Decoction Prevents BDL-Induced Liver Fibrosis Through Inhibition of Notch Signaling Activation
Huang Qi Decoction Prevents BDL-Induced Liver Fibrosis Through Inhibition of Notch Signaling Activation
复制标题
黄芪汤通过抑制Notch信号激活来预防BDL诱导的肝纤维化。
DOI：
10.1142/s0192415x17500070
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发表时间：
2017-01-01
影响因子：
5.7
通讯作者：
Liu, Ping
中科院分区：
文献类型：
--
作者：
Zhang, Xiao;Xu, Ying;Liu, Ping
Notch信号已被证明参与导管反应和纤维化。既往研究表明，黄芪汤（HQD）可预防胆汁淤积性肝纤维化（CLF）的进展。然而，HQD是否影响Notch信号通路尚不清楚。本研究采用胆总管结扎法（BDL）在大鼠体内建立CLF。第1周末，将大鼠随机分为模型组（即BDL）、HQD组和索拉非尼阳性对照组（sorafenib阳性对照组），疗程3周。组织染色观察胆管增生及肝纤维化情况。通过分析Notch-1、-2、-3和-4、Jagged (JAG) 1和Delta like (DLL)-1、-3和-4的表达来评估Notch信号通路的激活。结果显示，与BDL组相比，HQD显著减少肝组织胶原沉积和Hyp含量，抑制hsc的活化。此外，HQD显著降低TGF-[公式：见文]1和[公式：见文]- sma的蛋白和mRNA表达。相反，HQD显著增强Smad 7蛋白的表达。HQD还能抑制胆道上皮细胞的增殖，降低CK7、CK8、CK18、sry相关高迁移率群盒基因（SOX） 9、上皮细胞粘附分子（EpCAM） mRNA水平以及CK19、OV6阳性区域。此外，与BDL组相比，HQD组Notch-3、-4、JAG1、DLL-1、-3 mRNA和蛋白表达均显著降低。这些结果表明，HQD可能通过抑制Notch信号通路来预防胆汁性肝纤维化，可能是一种潜在的治疗胆汁淤积性肝病的方法。
Notch signaling has been demonstrated to be involved in ductular reactions and fibrosis. Previous studies have shown that Huang Qi Decoction (HQD) can prevent the progression of cholestatic liver fibrosis (CLF). However, whether HQD affects the Notch signaling pathway is unclear. In this study, CLF was established by common bile duct ligation (BDL) in rats. At the end of the first week, the rats were randomly divided into a model group (i.e., BDL), an HQD group, and a sorafenib positive control group (SORA) and were treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, and -4, Jagged (JAG) 1, and Delta like (DLL)-1, -3, and -4. The results showed that HQD significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs compared with the BDL group. In addition, HQD significantly decreased the protein and mRNA expressions of TGF-[Formula: see text]1 and [Formula: see text]-SMA. In contrast, HQD significantly enhanced expression of the Smad 7 protein. HQD also reduced biliary epithelial cell proliferation, and reduced the mRNA levels of CK7, CK8, CK18, SRY-related high mobility group-box gene (SOX) 9, epithelial cell adhesion molecule (EpCAM) and the positive areas of CK19 and OV6. In addition, the mRNA and protein expressions of Notch-3, -4, JAG1, and DLL-1, -3 were significantly reduced in the HQD compared to the BDL group. These results demonstrated that HQD may prevent biliary liver fibrosis through inhibition of the Notch signaling pathway, and it may be a potential treatment for cholestatic liver disease.