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黄芪多糖对肺转移前微环境中MMP、LOX、FN和VCAN表达的影响     被引量:3

Effect of Astragalus polysaccharides on the expression of MMP,LOX,FN and VCAN in pre-metastatic niche of lung

文献类型:期刊文献

中文题名:黄芪多糖对肺转移前微环境中MMP、LOX、FN和VCAN表达的影响

英文题名:Effect of Astragalus polysaccharides on the expression of MMP,LOX,FN and VCAN in pre-metastatic niche of lung

作者:明海霞[1,2,3,4,5];申明[1,2,3,4,5];王彦君[6];刘兆华[1,2,3,4,5];陈彦文[1];李杨[1,2,3,5];杨玲玲[1];梁乾坤[1]

第一作者:明海霞

机构:[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃中医药大学中西医结合基础学科,甘肃兰州730000;[3]甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,甘肃兰州730000;[4]甘肃中医药大学甘肃中医药研究中心,甘肃兰州730000;[5]甘肃中医药大学附属医院甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730000;[6]甘肃中医药大学附属医院重症医学科,甘肃兰州730000

第一机构:甘肃中医药大学基础医学院(敦煌医学研究所)

年份:2023

卷号:39

期号:16

起止页码:2363

中文期刊名:中国临床药理学杂志

外文期刊名:The Chinese Journal of Clinical Pharmacology

收录:CSTPCD;;北大核心:【北大核心2020】;CSCD:【CSCD2023_2024】;

基金:甘肃省“双一流”科研重点课题资助项目(GSSYLXM-05);甘肃省自然科学基金资助项目(20JR5RA178,20JR10RA320);甘肃省中医药研究中心开放课题资助项目(zyzx-2020-zx2);兰州市科技计划基金资助项目(2020-ZD-55,2021-1-96);甘肃中医药大学科学研究与创新基金资助项目(2020KCZD-4,2021KCZD-1);甘肃中医药大学中西医结合基础学科科研培育课题资助项目(2020-2021-12);甘肃中医药大学中西医结合学科研究生创新基金资助项目(8)。

语种:中文

中文关键词:黄芪多糖;肺癌;转移前微环境;金属基质蛋白酶;赖氨酰氧化酶;多功能蛋白聚糖;纤维连接蛋白

外文关键词:Astragalus polysaccharide;lung cancer;pre-metastatic niche;matrix metalloproteinases;lysyl oxidase;fibronectin;versican

摘要:目的研究黄芪多糖对肺转移前微环境(PMN)中金属基质蛋白酶-9(MMP-9)、赖氨酰氧化酶(LOX)、纤维连接蛋白(FN)和多功能蛋白聚糖(VCAN)表达的影响。方法将C57BL/6J小鼠随机分为正常组、模型组和低、中、高剂量实验组。除正常组外,其余各组尾静脉注射荧光素酶标记的Lewis肺癌细胞构建PMN模型。造模后次日开始给药,低、中、高剂量实验组分别给予50、100和200 mg·kg^(-1)黄芪多糖;模型组和正常组均给予0.9%NaCl。用小动物活体成像技术动态监测小鼠体内肿瘤转移情况,用逆转录荧光定量聚合酶链反应法检测肺组织中MMP-9、LOX、FN和VCAN基因的表达水平。结果小动物活体成像显示,与模型组相比,低、中、高剂量实验组小鼠肺组织的荧光表达均有不同程度的降低。中、高剂量实验组和模型组、正常组的MMP-9 mRNA分别为6.23±0.29、4.77±0.18、15.12±1.28和1.00±0.10,LOX mRNA分别为8.27±0.39、7.24±1.50、46.88±4.20和1.00±0.07,FN mRNA分别为4.40±0.24、3.28±0.23、63.79±1.30和1.00±0.13,VCAN mRNA分别为2.28±0.05、2.24±0.12、12.93±0.43和1.00±0.05。中、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(P<0.01,P<0.05)。结论黄芪多糖可能通过下调LOX、MMP-9、FN和VCAN表达,从而抑制肺PMN的形成。
Objective To investigate the effects of Astragalus polysaccharide(APS)on matrix metalloproteinases-9(MMP-9),lysyl oxidase(LOX),fibronectin(FN)and versican(VCAN)in pre-metastatic niche of lung.Methods C57BL/6J mice were randomly divided into normal group,model group and experimental-L,-M,-H groups.Except for the normal group,the PMN model was constructed by tail vein injection of luciferase labeled Lewis lung cancer cells in each group.The drug administration was started on the next day after modeling,and 50,100 and 200 mg·kg^(-1)APS were given to the experimental-L,-M,-H groups,respectively;0.9%NaCl was given to the model and normal groups.The tumor metastasis in mice was dynamically monitored by bioluminescent imaging technology,and the expression levels of MMP-9,LOX,FN and VCAN genes in lung tissue were detected by reverse transcription quantitative polymerase chain reaction.Results Bioluminescent imaging showed that the fluorescence expressions in the lung tissue of mice in the experimental-L,-M,-H groups were reduced to different degrees compared to the model group.The MMP-9 mRNA expression levels of the experimental-M,-H groups,model group and normal group were 6.23±0.29,4.77±0.18,15.12±1.28 and 1.00±0.10;the LOX mRNA expression levels were 8.27±0.39,7.24±1.50,46.88±4.20 and 1.00±0.07;the FN mRNA expression levels were 4.40±0.24,3.28±0.23,63.79±1.30 and 1.00±0.13;the VCAN mRNA expression levels were 2.28±0.05,2.24±0.12,12.93±0.43 and 1.00±0.05,respectively.The differences of above indexes in the experimental-M,-H groups were statistically significant when compared with those of model group(P<0.01,P<0.05).Conclusion APS may inhibit PMN of lung formation by down-regulating the expressions of LOX,MMP-9,FN and VCAN.

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