氧化苦参碱通过免疫调节保护刀豆蛋白A诱导的小鼠免疫性肝损伤  

Oxymatrine Protects Against Liver Injury Induced by Con A in Mice Through Suppressing Host Immune Response

作　　者：桑秀秀 王睿林[3] 韩延忠 崔鹤蓉[1,2] 尹萍[2] 贺兰芝 刘慧敏[1,2] 刘士敬[3] 肖小河[2] 柏兆方[2] 

机构地区：[1]承德医学院,河北承德067000 [2]解放军第302医院全军中医药研究所,北京100039 [3]解放军第302医院中西医结合肝病诊疗与研究中心,北京100039

出　　处：《中国实验方剂学杂志》2017年第6期125-130,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81330090)

摘　　要：目的:本文旨在研究氧化苦参碱(OMT)对刀豆蛋白A(Con A)所致小鼠免疫性肝损伤的保护作用。方法:Balb/C小鼠随机分为5组,分别为正常组,模型组,氧化苦参碱低、高剂量(60,120 mg·kg-1)组和双环醇(156 mg·kg-1)阳性药组。连续给药5 d,末次给药30 min后,除正常组外,其余各组均尾静脉注射Con A(15 mg·kg-1)建立肝损伤模型。造模8 h后,检测血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),总胆红素(TBIL)的表达。采用Luminex多因子检测的方法,检测血清干扰素-γ(IFN-γ),肿瘤坏死因子-α(TNF-α),白细胞介素-4(IL-4),IL-6,IL-10,IL-27表达,苏木精-伊红(HE)染色观察肝组织病理改变。流式细胞术检测小鼠脾淋巴细胞CD4+IL-17A的表达,CD4+CD25+Fox P3+调节性T细胞(Treg)亚群的比例。结果:与正常组比较,Con A模型组ALT,AST,TBIL表达明显增高(P<0.05,P<0.01)。与模型组比较,双环醇和OMT低高剂量组均可明显降低ALT活性(P<0.05,P<0.01)。OMT高剂量可明显抑制AST表达(P<0.05),OMT低高剂量均可抑制TBIL表达(P<0.05),其余各组无统计学差异。各给药组均能不同程度缓解肝脏病理改变,减少炎性细胞浸润。OMT高剂量组血清IL-10,IL-27水平与模型组比较显着升高(P<0.05)。流式细胞术检测结果显示,OMT高剂量组可明显降低CD4+IL-17A表达(P<0.05),上调CD4+CD25+Fox P3+Treg比例(P<0.05)。结论:OMT对Con A诱导小鼠免疫性肝损伤具有较好的保护作用,抑制CD4+IL-17A的表达,上调CD4+CD25+Fox P3+Treg比例可能是其主要的作用机制。Objective： To investigate the immunomodulatory effect of oxymatrine on concanavalin A（ Con A）-induced liver injury in mice. Method： In the present study,Balb /C mice were randomly divided into five groups： normal group,model group,low and high-dose oxymatrine groups（ 60,120 mg·kg- 1） and bicyclol group（ 156 mg·kg- 1）. The mice in the treated groups were administered with oxymatrine（ intraperitoneally） or bicyclol（ orally） for 5 consecutive days. 30 min after the last medication,all the mice except the normal group were injected with 15 mg·kg- 1of Con A intravenously to establish liver injury models. 8 hours later,blood samples were taken to test the levels of alanine transaminase（ ALT）, aspartate aminotransferase（ AST）,and total bilrubin（ TBIL） in serum,and the liver tissues were taken for HE-staining to evaluate the histopathology changes.The expression levels of serum cytokines interferon-γ（ IFN-γ）,tumour necrosis factor-α（ TNF-α）,interleukin-4（ IL-4）,interleukin-6（ IL-6）,interleukin-10（ IL-10） and interleukin-27（ IL-27） were measured by luminex.Spleen lymphocytes were isolated and the expression levels of CD4＋IL-17 A and the percentage of CD4＋CD25＋Fox P3＋Treg were tested by flow cytomerty. Results showed that,after con-A injection,the expression levels of ALT,AST and TBIL were increased（ P〈0. 05,P〈0. 01） as compared with the normal group. As compared with the model group,bicyclol and oxymatrine（ 60,120 mg·kg- 1） could markedly decrease the activity of ALT（ P〈0. 05,P〈0. 01）; oxymatrine at 120 mg·kg- 1could significantly decrease the levels of AST（ P〈0. 05）,and oxymatrine at both 60,120 mg·kg- 1could decrease the levels of TBIL（ P〈0. 05）. There were no statistical differences in other groups. All treatment groups could relieve the liver pathological changes to different degrees,and reduce the infiltration of inflammatory cells. After treatment with high dose OMT,the levels of IL-10 and IL-27 were signi

关 键 词：氧化苦参碱 刀豆蛋白A 白细胞介素 调节性T细胞 

分 类 号：R285.5[医药卫生—中药学]