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。
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 hepaticα-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 ofα-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.
作者
王祖文
沈以红
黄先智
丁晓雯
WANG Zuwen;SHEN Yihong;HUANG Xianzhi;DING Xiaowen(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;State Key Laboratory of Silkworm Genome Biology,Chongqing 400716,China)
出处
《食品科学》
EI
CAS
CSCD
北大核心
2021年第3期173-178,共6页
Food Science
基金
现代农业产业技术体系建设专项(CARS-18)。
