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柴胡皂苷b2对LPS/GalN诱导的小鼠急性肝损伤炎症和能量代谢的影响

Effects of saikosaponin b2 on inflammation and energy metabolism in mice with acute liver injury induced by LPS/GalN
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摘要 该研究旨在探讨柴胡皂苷b2(SS-b2)对注射脂多糖/氨基半乳糖(LPS/Gal N)诱导的小鼠急性肝损伤炎症因子的调控和对能量代谢的影响。将小鼠随机分为空白对照组(等量生理盐水),模型组(100μg·kg-1LPS+400 mg·kg-1Gal N),SS-b2低、中、高剂量组(5,10,20 mg·kg-1·d-1)和阳性对照组(地塞米松,10 mg·kg-1)。除空白对照组外,其余各组每天腹腔注射LPS/Gal N建立急性肝损伤小鼠模型。计算脏器指数;血清生化指标检测ALT和AST的含量和肝脏ATP酶(Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶)活性的变化;酶联免疫吸附(ELISA)法检测血清中TNF-α,IL-1β,IL-6的含量;微量酶标法测定肝脏LDH的含量;HE染色观察肝组织病理学变化;免疫组化法测定LDH-A的蛋白表达;Western blot法检测肝脏Sirt-6和NF-κB蛋白表达情况。结果显示,与模型组相比,SS-b2高剂量组小鼠脏器指数均有明显变化(P<0. 05);SS-b2中、高剂量组能明显降低肝损伤小鼠血清中ALT,AST,TNF-α,IL-1β,IL-6的水平及LDH活性(P<0. 01),随着SS-b2剂量的增加,小鼠肝脏病变范围减少,损伤程度减轻,各剂量组能够显著增强小鼠肝脏Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶的活性(P<0. 01);SS-b2中、高剂量组能够显著下调肝组织NF-κB的蛋白表达(P<0. 01),同时,各剂量组能够显著提高急性肝损伤小鼠肝脏中Sirt-6蛋白表达量(P<0. 01)。综上,SS-b2对LPS/Gal N诱导的小鼠急性肝损伤具有显著的保护作用,该作用可能与其下调NF-κB蛋白表达以及上调Sirt-6蛋白表达改善炎症损伤以及能量代谢有关。 To study the effects of saikosaponin b2(SS-b2)on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine(LPS/Gal N)induced acute liver injury in mice.Mice were randomly divided into normal group(equal amount of normal saline),model group(100 g·kg-1 LPS and 400 mg·kg-1 Gal N),low,medium,high dose group of SS-b2(SS-b25,10,20 mg·kg-1·d-1)and positive control group(dexamethasone,10 mg·kg-1).All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model.The organ indexes were calculated.The levels of serum transaminases(ALT and AST)and the activities of ATPase(Na+-K+-ATPase,Ca2+-Mg2+-ATPase)in liver were detected.The activity of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were determined by the enzyme-linked immunosorbent assay(ELISA).The contents of lactate dehydrogenase(LDH)in liver were determined by micro-enzyme method.HE staining was used to observe the histopathological changes of the liver.Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A(LDH-A).The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot.According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2(P<0.05).The level of ALT,AST,TNF-α,IL-1β,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2(P<0.01).With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased.The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group(P<0.01).The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group(P<0.01).Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased
作者 有曼 李瑞芳 高子涵 李原野 刘唯夷 王建刚 王红伟 李三强 YOU Man;LI Rui-fang;GAO Zi-han;LI Yuan-ye;LIU Wei-yi;WANG Jian-gang;WANG Hong-wei;LI San-qiang(Medical College,Henan University of Science and Technology,Luoyang471023,China;School of Nursing,Henan University of Science and Technology,Luoyang471023,China)
出处 《中国中药杂志》 CAS CSCD 北大核心 2019年第14期2966-2971,共6页 China Journal of Chinese Materia Medica
基金 国家自然科学基金项目(81201558) 河南省科技攻关重点项目(142102310137) 洛阳市科技计划医疗卫生项目(1603001A-3).
关键词 柴胡皂苷b2 急性肝损伤 NF-ΚB Sirt-6 炎症 能量代谢 saikosaponin b2 acute liver injury NF-κB Sirt-6 inflammation energy metabolism
作者简介 通讯作者:李瑞芳,博士,硕士生导师,Tel:(0379)64820862,E-mail:ylliruifang@163.com;有曼,硕士研究生,E-mail:youman_0906@163.com
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