占敏霞;杜伟;李恒华;罗金萍;梅小利;涂如霞;张莉;
ZHAN Min-xia;DU Wei;LI Heng-hua;LUO Jin-ping;MEI Xiao-li;TU Ru-xia;ZHANG Li;Institute of Chinese Pharmacology and Toxicology, Chongqing Academy of Chinese Materia Medica;

• 1:重庆市中药研究院药理毒理研究所

摘要(Abstract)：

研究双氢青蒿素与火把花配伍对迟发型超敏反应小鼠的免疫抑制作用及可能的作用机制。通过建立迟发型超敏反应(delayed-type hypersensitivity,DTH)小鼠模型,观察双氢青蒿素与火把花配伍对DTH小鼠的免疫抑制效应;苏木素-伊红(HE)染色观察耳组织病理学改变及单核细胞浸润程度;酶联免疫吸附测定(ELISA)法检测血清中γ干扰素(interferon,IFN-γ)水平;免疫组化法检测小鼠右耳细胞黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1)表达水平,蛋白质免疫印迹(Western blot)法检测右耳磷酸化p38丝裂酶原激活蛋白激酶(p38 phospho mitogen activated protein kinase,p-p38 MAPK)蛋白的活性表达情况。结果显示,与正常组比较,模型组小鼠耳肿胀度、胸腺/脾脏指数、单核细胞浸润计数及浸润程度明显升高,血清IFN-γ含量显著升高;与模型组比较,双氢青蒿素与火把花配伍组小鼠耳肿胀度、胸腺/脾脏指数显著降低,单核细胞浸润计数及浸润程度明显减轻,血清中IFN-γ含量显著降低,右耳p-p38 MAPK和ICAM-1蛋白表达水平显著下调。表明青蒿素与火把花配伍能够明显抑制DTH反应,其可能通过抑制p38 MAPK磷酸化活性的表达,调节相关炎症因子IFN-γ的产生和分泌,进一步降低ICAM-1的表达,从而发挥免疫抑制作用。
The aim of this paper was to investigate the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in mice with delayed hypersensitivity and explore its possible mechanism. The delayed-type hypersensitivity(DTH) model in mice was established to observe the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in DTH mice. ELISA assay was used to detect the contents of interferon(IFN-γ); histopathological changes and degree of mononuclear infiltration of right ear tissues were examined by HE staining; the expression level of intercellular cell adhesion molecule-1(ICAM-1) in the right ear of mice was detected by immunohistochemistry; the protein expression levels of p38 phospho mitogen activated protein kinase(p-p38 MAPK) was detected by Western blot analysis. As compared with the control group, the degree of ear swelling, thymus/spleen index, serum IFN-γ as well as the number and degree of infiltration of monocytes were significantly increased in the model group. As compared with the model group, the degree of ear swelling and thymus/spleen index of the mice in the combination group were significantly reduced; the number and degree of infiltration of monocytes were significantly relieved; the serum levels of IFN-γ and the expression levels of p-p38 MAPK and ICAM-1 proteins in the right ear were also significantly reduced. The combination of dihydroartemisinin and Huobahua can significantly inhibit the DTH response, and it may regulate the production and secretion of related inflammatory factor IFN-γ by inhibiting the phosphorylation activity of p38 MAPK, thereby further reducing the expression of ICAM-1 and thus exerting the immunosuppressive effect.

关键词(KeyWords)： 双氢青蒿素;火把花;配伍;免疫抑制;p-p38 MAPK;ICAM-1
dihydroartemisinin;Huobahua;combination;immunosuppression;p-p38 MAPK;ICAM-1

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2017ZX09101002-002-004);; 重庆市科技计划项目(cstc2018jxjl-jbky120006);; 科研机构绩效激励引导专项(cstc2019jxjl10001)

作者(Authors): 占敏霞;杜伟;李恒华;罗金萍;梅小利;涂如霞;张莉;
ZHAN Min-xia;DU Wei;LI Heng-hua;LUO Jin-ping;MEI Xiao-li;TU Ru-xia;ZHANG Li;Institute of Chinese Pharmacology and Toxicology, Chongqing Academy of Chinese Materia Medica;

DOI: 10.19540/j.cnki.cjcmm.20200708.401

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