丹参多糖对免疫性肝损伤小鼠肝脏过氧化指标、炎症细胞因子和ICAM-1的影响
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摘要
将SPF级雄性昆明小鼠随机分成正常对照组,LPS模型组,丹参多糖低、中、高剂量组和阳性药物对照组。灌胃相应药物12 d后,腹腔注射LPS和D-GalN建立小鼠免疫性肝损伤模型。检测各组小鼠肝组织中SOD、MDA、GSH-Px水平,比较造模1,3 h后各组小鼠肝组织中IL-1β、IL-6、TNF-α的含量变化以及测定肝组织ICAM-1蛋白的表达水平。结果显示,与正常对照组比较,LPS模型组小鼠肝组织中MDA含量显著升高,SOD、GSH-Px活性显著降低, IL-1β、IL-6、TNF-α含量以及ICAM-1蛋白表达水平均显著升高(P<0.01);与LPS模型组相比,丹参多糖各剂量组和阳性药物对照组小鼠肝组织中MDA含量显著降低,SOD、GSH-Px活性显著升高,IL-1β、IL-6、TNF-α含量以及ICAM-1蛋白表达水平均显著降低(P<0.05或P<0.01);各用药组之间相比较,丹参多糖中、高剂量组和阳性药物对照组调控过氧化指标、炎症细胞因子和ICAM-1效果最显著(P<0.05或P<0.01)。结果表明,丹参多糖具有明显缓解小鼠免疫性肝损伤的作用,其机制可能与拮抗肝脏脂质过氧化反应,降低肝组织中炎症细胞因子含量及ICAM-1蛋白表达有关。
Kunming mice were randomly divided into six groups:the normal control group,LPS model group,positive drug control group and low,medium and high dose of salvia miltiorrhiza polysaccharide(SMPS) protection group.Each group of mice were given the same amount of normal saline or the corresponding drugs.After intragastric administration for 12 days,the model of immunological liver injury in mice was established by injecting intraperitoneally LPS and D-GalN.Detected the levels of SOD,MDA and GSH-Px of IL-1β,IL-6 and TNF-α,and of expression of ICAM-1 in the liver tissue in mice of each group.Compared with the normal control group,the content of MDA in the liver tissue of the LPS model group was increased significantly,the activity of SOD and GSH-Px was decreased significantly,the contents of IL-1β,IL-6,TNF-α and the expression level of ICAM-1 were increased significantly(P<0.01).Compared with LPS model group,the content of MDA in liver tissue of three dose groups of SMPS and positive drug control group was decreased significantly,the activity of SOD and GSH-Px was increased significantly,the contents of IL-1β,IL-6 TNF-α and the expression level of ICAM-1 were decreased significantly(P<0.05 or P<0.01),especially the medium and high dose of SMPS groups and positive drug control group(P<0.05 or P<0.01).SMPS can obviously relieve the immunological liver injury in mice.The mechanism may be related to the inhibition of the peroxidation,inflammatory cytokines and ICAM-1.
Kunming mice were randomly divided into six groups:the normal control group,LPS model group,positive drug control group and low,medium and high dose of salvia miltiorrhiza polysaccharide(SMPS) protection group.Each group of mice were given the same amount of normal saline or the corresponding drugs.After intragastric administration for 12 days,the model of immunological liver injury in mice was established by injecting intraperitoneally LPS and D-GalN.Detected the levels of SOD,MDA and GSH-Px of IL-1β,IL-6 and TNF-α,and of expression of ICAM-1 in the liver tissue in mice of each group.Compared with the normal control group,the content of MDA in the liver tissue of the LPS model group was increased significantly,the activity of SOD and GSH-Px was decreased significantly,the contents of IL-1β,IL-6,TNF-α and the expression level of ICAM-1 were increased significantly(P<0.01).Compared with LPS model group,the content of MDA in liver tissue of three dose groups of SMPS and positive drug control group was decreased significantly,the activity of SOD and GSH-Px was increased significantly,the contents of IL-1β,IL-6 TNF-α and the expression level of ICAM-1 were decreased significantly(P<0.05 or P<0.01),especially the medium and high dose of SMPS groups and positive drug control group(P<0.05 or P<0.01).SMPS can obviously relieve the immunological liver injury in mice.The mechanism may be related to the inhibition of the peroxidation,inflammatory cytokines and ICAM-1.
引文
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[12] 张引强.中药荣肝合剂对刀豆蛋白A介导的免疫性肝损伤降酶效应的机制研究[D].北京:中国中医科学院,2010.
[13] 汤新慧,高静,王燕萍,等.榄仁叶氯仿提取物的护肝作用及其对肝脏IL-6表达的抑制作用[J].中国中药杂志,2003(12):70-74.
[14] COIMBRA R,MELBOSTAD H,LOOMIS W,et al.LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition:effects on proinflammatory mediators,metalloproteinases,NF-kappaB,and ICAM-1 expression[J].Trauma,2006,60(1):115-125.
[15] ZHEN M C,WANG Q,HUANG X H,et al.Green tea polyphenolepigallocatechin-3-gallate inhibits oxidative damageand preventive effects on carbon tetrachloride-induced hepatic fibrosis[J].J Nutr Biochem,2007,18:795-805.
[16] 万涛,朱冠保.NF-κB、ICAM-1和炎症细胞因子在急性胰腺炎肝损伤中的作用[J].国外医学(临床生物化学与检验学分册),2005(12):913-915.
[17] 钟振东,苏娟,何永亮.黄芪多糖治疗免疫性肝损伤作用机理研究[J].时珍国医国药,2013,24(5):1155-1156.
[18] 焦西英,杨浩,钱新宏,等.EGCG对过氧化氢所致神经元过氧化损伤的保护作用[J].解剖学研究,2008(6):401-403.
[2] 冯玲玲,周吉源.丹参的研究现状与应用前景[J].中国野生植物资源,2004(2):4-7.
[3] 卢艳娴,宋雨鸿,徐霞,等.丹参多糖对急性肝损伤小鼠肝窦内皮细胞窗孔的影响[J].广州医科大学学报,2015,43(6):9-12.
[4] 陈华栋.小鼠免疫性肝损伤模型的研究进展[C]//中国药理学会.2010年度全国医药学术论文交流会暨临床药学与药学服务研究进展培训班论文集.[S.l.]:中国药理学会,2010.
[5] ANDREW F G,SLATER C,STEFAN I,et al.The role of intracellular oxidants in apoptosis[J].Biochim Biophys Acta,1995,1271(1):59-62.
[6] 张笑天,郑晓瑛.氧化自由基清除剂超氧化物歧化酶与疾病[J].中国公共卫生,2014,30(10):1349-1352.
[7] 刘可心.大豆皂苷对小鼠亚急性肝损伤的保护作用及机制研究[D].吉林延吉:延边大学,2014.
[8] 王海颖,张晋军,张艳敏,等.芍药红花煎剂对肝损伤细胞氧自由基及凋亡因子影响研究[J].中华中医药学刊,2016,34(6):1348-1350.
[9] 彭维兵,李国强,孙伟之,等.2种新型18 β-甘草次酸修饰物对四氯化碳致小鼠肝损伤的保护作用[J].中国海洋大学学报(自然科学版),2011,41(Z1):133-136.
[10] 李伦,钟伟超,梁伟海,等.栀子大黄汤对四氯化碳致小鼠急性肝损伤的保护作用[J].中国实验方剂学杂志,2016,22(12):108-112.
[11] HAN C,YANG J,SONG P,et al.Effects of salvia miltiorrhiza polysaccharides on lipopolysaccharide-induced inflammatory factor release in RAW264.7 cells[J].Interferon Cytokine Res,2018,38(1):29-37.
[12] 张引强.中药荣肝合剂对刀豆蛋白A介导的免疫性肝损伤降酶效应的机制研究[D].北京:中国中医科学院,2010.
[13] 汤新慧,高静,王燕萍,等.榄仁叶氯仿提取物的护肝作用及其对肝脏IL-6表达的抑制作用[J].中国中药杂志,2003(12):70-74.
[14] COIMBRA R,MELBOSTAD H,LOOMIS W,et al.LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition:effects on proinflammatory mediators,metalloproteinases,NF-kappaB,and ICAM-1 expression[J].Trauma,2006,60(1):115-125.
[15] ZHEN M C,WANG Q,HUANG X H,et al.Green tea polyphenolepigallocatechin-3-gallate inhibits oxidative damageand preventive effects on carbon tetrachloride-induced hepatic fibrosis[J].J Nutr Biochem,2007,18:795-805.
[16] 万涛,朱冠保.NF-κB、ICAM-1和炎症细胞因子在急性胰腺炎肝损伤中的作用[J].国外医学(临床生物化学与检验学分册),2005(12):913-915.
[17] 钟振东,苏娟,何永亮.黄芪多糖治疗免疫性肝损伤作用机理研究[J].时珍国医国药,2013,24(5):1155-1156.
[18] 焦西英,杨浩,钱新宏,等.EGCG对过氧化氢所致神经元过氧化损伤的保护作用[J].解剖学研究,2008(6):401-403.