食品科学 ›› 2021, Vol. 42 ›› Issue (3): 173-178.doi: 10.7506/spkx1002-6630-20191218-215

• 营养卫生 • 上一篇    下一篇

桑叶生物碱对肝纤维化小鼠的改善作用及机制

王祖文，沈以红，黄先智，丁晓雯   

  1. （1.西南大学食品科学学院，重庆市农产品加工及贮藏重点实验室，食品科学与工程国家级实验教学示范中心，重庆 400716；2.西南大学 家蚕基因组生物学国家重点实验室，重庆 北碚 400716）
  • 发布日期:2021-02-25
  • 基金资助:
    现代农业产业技术体系建设专项（CARS-18）

Effect and Mechanism of Mulberry Leaf Alkaloid on Improving Hepatic Fibrosis in Mice

WANG Zuwen, SHEN Yihong, HUANG Xianzhi, DING Xiaowen   

  1. (1. Chongqing Key Laboratory of Processing and Storage of Agricultural Products, National Demonstration Center for Experimental Food Science and Technology Education, College of Food Science, Southwest University, Chongqing 400716, China; 2. State Key Laboratory of Silkworm Genome Biology, Chongqing 400716, China)
  • Published:2021-02-25

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摘要： 目的：观察桑叶生物碱对转化生长因子-β1（transforming growth factor-β1，TGF-β1）/Smads信号通路及基质金属蛋白酶-13（matrix metalloproteinase-13，MMP-13）、基质金属蛋白酶抑制剂-1（inhibitor of metalloproteinase-1，TIMP-1）mRNA表达的调节作用，探讨桑叶生物碱改善小鼠肝纤维化的作用机制。方法：采用腹腔注射体积分数10% CCl4 橄榄油溶液（5 mL/kg mb）联合高脂饮食诱导小鼠肝纤维化模型。造模8 周后，正常对照组和模型组给予蒸馏水，低、中、高剂量组分别灌胃50、100、200 mg/kg mb剂量的桑叶生物碱，阳性药物组给予100 mg/kg mb水飞蓟宾，持续45 d。采用酶联免疫试剂盒测定各组小鼠肝组织α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、I型胶原蛋白（collagen I，Col I）及III型胶原蛋白（collagen III，Col III）含量；采用实时定量聚合酶链式反应测定肝组织TGF-β1、Smad3、Smad4、Smad7、MMP-13、TIMP-1 mRNA表达水平。结果：与模型组比，灌胃高剂量桑叶生物碱（200 mg/kg mb）的小鼠肝组织中α-SMA、Col I、Col III含量分别降低19.55%、19.93%、13.84%（P＜0.05）；TGF-β1、Smad3、Smad4、TIMP-1 mRNA表达水平分别下降59.04%、56.73%、50.70%、49.09%（P＜0.05），Smad7、MMP-13 mRNA表达水平分别上升48.29%、25.72%（P＜0.05）。结论：桑叶生物碱能改善小鼠肝纤维化，其机制可能是对TGF-β1/Smads信号通路相关因子和TIMP-1、MMP-13的基因表达具有调控作用。

关键词: 桑叶生物碱；肝纤维化；转化生长因子-β1/Smads信号通路；基质金属蛋白酶-13；基质金属蛋白酶抑制剂-1

Abstract: Objective: To investigate the regulatory effects of mulberry leaf alkaloid on the transforming growth factor-β1 (TGF-β1)/Smads pathway and the expression of matrix metalloproteinase-13 (MMP-13) and inhibitor of metalloproteinase-1 (TIMP-1), and to explore its action mechanism in alleviating hepatic fibrosis in mice. Methods: Hepatic fibrosis in mice was induced by intraperitoneal injection of 10% (V/V) CCl4 in olive oil at a dose of 5 mL/kg mb every other day combined with feeding a high-fat diet for 8 consecutive weeks. Thereafter, the mice in the control and model groups were given distilled water, those in the low-, medium- and high-dose treatment groups were intragastrically administered with 50, 100 and 200 mg/kg mb mulberry leaf alkaloid, and those in the positive drug group were gavaged with 100 mg/kg of silibinin for 45 days. The contents of hepatic α-smooth muscle actin (α-SMA), collagen I (Col I) and collagen III (Col III) in mice were determined by enzyme-linked immunosorbent assay (ELISA) kits, and the mRNA expression levels of TGF-β1, Smad3, Smad4, Smad7, MMP-13 and TIMP-1 were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Results: Compared with the model group, the contents of α-SMA, collagen I and collagen III in the high-dose group decreased by 19.55%, 19.93% and 13.84% (P < 0.05), respectively. Similarly, the mRNA expression levels of TGF-β1, Smad3, Smad4 and TIMP-1 significantly decreased by 59.04%, 56.73%, 50.70% and 49.09% (P < 0.05), respectively. Moreover, Smad7 and MMP-13 mRNA expression levels increased by 48.29% and 25.72% (P < 0.05), respectively. Conclusion: Mulberry leaf alkaloids can improve hepatic fibrosis in mice, and its underlying mechanism may be related to the regulation of the TGF-β1/Smads signaling pathway related factors and TIMP-1 and MMP-13 mRNA expression.

Key words: mulberry leaf alkaloid; hepatic fibrosis; transforming growth factor-β1/Smads signaling pathway; matrix metalloproteinase-13; inhibitor of metalloproteinase-1

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