| 引用本文： |
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罗辉,孔瑞,王楠,等.橘皮素通过抑制Notch信号通路干预小鼠肝纤维化进程[J].同济大学学报（医学版）,2018,39(5):11-16. [点击复制]
- LUO Hui,KONG Rui,WANG Nan,et al.Protective effect of tangeretin on liver fibrosis via inhibiting the activation of Notch pathway[J].同济大学学报（医学版）,2018,39(5):11-16. [点击复制]
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| 摘要: |
| 目的 探讨橘皮素对胆汁淤积性肝纤维化小鼠模型的治疗机制。方法 将45只C57BL/6J小鼠随机分为假手术组（n=10）、胆总管结扎手术（biliary duct ligation, BDL）模型组（n=15）、橘皮素治疗组（n=10）及单纯橘皮素用药组（n=10）。药物治疗组中，BDL手术10d后开始橘皮素灌胃，模型建立30d后采血处死各组小鼠并留取肝组织。通过H-E染色、Masson及天狼星红染色分析各组小鼠肝组织纤维化程度；采用酶联免疫吸附实验（ELISA）检测各组小鼠血清肝功能指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)及纤维化指标透明质酸(HA)、层粘连蛋白(LN)水平；通过蛋白质印迹、荧光定量聚合酶链反应(PCR)、免疫组织化学方法检测各组小鼠肝组织中羟脯氨酸(Hyp)含量及Notch通路各组分表达量变化；通过免疫组化法检测肝纤维经典通路TGF-β1/smads通路各组分表达量变化。结果 造模30d后，与BDL模型组相比，橘皮素治疗组小鼠肝纤维化假小叶减少，纤维化病理评分值低（P<0.05）；胶原纤维沉积减少（P<0.05），Ⅰ型胶原纤维总量减少（P<0.05）；小鼠肝功能指标ALT、AST明显降低（P<0.05），纤维化指标HA、LN降低（P<0.05）；Hyp含量降低（P<0.05），Notch信号通路组分Notch1、RBPJ、Hes1、Hey1蛋白及RNA表达量均下调（均P<0.05）；肝纤维化TGF-β1/smads经典通路组分TGF-β1、smad2及smad3表达量下调（均P<0.05）。结论 橘皮素作为Notch信号通路抑制剂可通过与TGF-β1/smads通路相互作用延缓肝纤维化进程。 |
| 关键词: 胆总管结扎手术 橘皮素 肝纤维化 Notch信号通路 |
| DOI：10.16118/j.1008-0392.2018.05.003 |
| 投稿时间：2018-01-29 |
| 基金项目:国家自然科学基金（81770518） |
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| Protective effect of tangeretin on liver fibrosis via inhibiting the activation of Notch pathway |
| LUO Hui,KONG Rui,WANG Nan,LU Jie |
| (Dept. of Gastroenterology, Tenth People's Hospital, Shanghai 200072, China) |
| Abstract: |
| Objective To explore the therapeutic effect of tangeretin on the liver fibrosis. Methods A total of 45 C57BL/6J mice were randomly divided into 4 groups, including sham operation group(n=10), biliary duct ligation(BDL) model group(n=15), tangeretin treatment group(n=10), and pure tangeretin group(n=10). Mice in tangeretin treatment group were fed with tangeretin 10d after surgery. All animals were sacrificed 30d later, the liver specimens and serum samples were collected. The results were determined using enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining. Results Compared to BDL model group, the serum levels of ALT, AST, LN, HA, and Hyp were decreased; the pathological changes were ameliorated in tangeretin treatment group. The expression of Notch signaling pathway proteins Notch1, RBPJ, Hes1, Hey1 as well as the expression of TGF-β1/smads pathway proteins TGF-β1, smad2, smad3 were decreased in tangeretin treatment group. Conclusion As the Notch signaling pathway inhibitor, tangeretin exerts the protective effect by interacting with the activation of TGF-β1/smads signal on the process of liver fibrosis, indicating that the application of this natural product will provide new ideas for clinical treatment of liver fibrosis. |
| Key words: bile duct ligation tangeretin liver fibrosis Notch signaling pathway |
