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麻黄细辛附子汤对肾阳虚外感证模型小鼠 TLRs 应答及 Cyt-CO

        介导的凋亡调控的影响                          Δ


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        邢淑雁 ,范珊珊 ,于钦辉 ,马青云 ,孙启慧 ,杨 勇                         2,3,4 ,容 蓉 (1.山东中医药大学药学院,济南
                                  1
        250355;2.山东中医药大学实验中心,济南 250355;3.山东省高校中医药抗病毒协同创新中心,济南 250355;
        4.山东省中医药抗病毒工程研究中心,济南 250355)
        中图分类号 R285          文献标志码 A          文章编号 1001-0408(2021)06-0669-07
        DOI  10.6039/j.issn.1001-0408.2021.06.05

        摘  要   目的:研究麻黄细辛附子汤对肾阳虚外感证模型小鼠Toll样受体(TLRs)应答及细胞色素C氧化酶(Cyt-CO)介导的凋亡
        调控的影响。方法:将48只雄性Balb/c小鼠随机分为正常组(n=12)和造模组(n=36)。造模组小鼠采用腹腔注射苯甲酸雌二醇
        溶液(8 mg/kg)+滴鼻接种甲型H1N1流感病毒(20 μL/只)的方法建立肾阳虚外感复合模型。然后将造模成功的小鼠随机分为模
        型组、阳性药组(磷酸奥司他韦胶囊,0.195 g/kg)和麻黄细辛附子汤组(1.802 g/kg,以生药总量计),每组12只。各给药组小鼠灌胃
        相应药液,正常组和模型组小鼠灌胃等体积生理盐水;灌胃体积均为20 mL/kg,每天1次,连续给药6天。给药期间,每天测量小鼠
        体质量、肛温,并计算其初始体质量百分率;末次给药后,计算其脏器(脾、胸腺、肺)指数,观察其肺组织病理学变化,检测其肺组织
        中甲型H1N1流感病毒的病毒载量(以M基因mRNA表达水平反映)以及心脏组织中TLR3、TLR7、髓样分化因子(MyD88)、胱天
        蛋白酶3(Caspase-3)mRNA表达水平和Cyt-CO活性、细胞色素C(Cyt-C)含量。结果:与正常组比较,模型组小鼠的初始体质量
        百分率、肛温持续降低(P<0.05);脾指数、胸腺指数均显著降低(P<0.05),肺指数显著升高(P<0.05);肺组织病变严重;肺组织中
        病毒载量和心脏组织中TLR3、TLR7、MyD88、Caspase-3 mRNA表达水平及Cyt-C含量均显著升高(P<0.05或P<0.01),心脏组织
        中Cyt-CO活性显著降低(P<0.01)。与模型组比较,麻黄细辛附子汤组小鼠的初始体质量百分率、肛温自给药第4天起呈上升趋
        势(P<0.05或P<0.01);脾指数、胸腺指数均显著升高(P<0.05),肺指数均显著降低(P<0.05);肺组织病理损伤明显改善;肺组
        织中病毒载量和心脏组织中TLR3、Caspase-3 mRNA表达水平和Cyt-C含量均显著降低(P<0.05或P<0.01),心脏组织中Cyt-CO
        活性显著升高(P<0.01)。结论:麻黄细辛附子汤对肾阳虚外感病证模型小鼠具有改善作用,这可能与其可抑制 TLRs 应答和
        Cyt-CO介导的凋亡调控途径有关。
        关键词 麻黄细辛附子汤;肾阳虚外感证;细胞色素C氧化酶;细胞色素C;凋亡;Toll样受体;小鼠

        Effects of Mahuang Xixin Fuzi Decoction on TLRs Response and Cyt-CO-mediated Apoptosis Regulation
        in Mice with Influenza Disease of Kidney-yang Deficiency
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        XING Shuyan ,FAN Shanshan ,YU Qinhui ,MA Qingyun ,SUN Qihui ,YANG Yong          2,3,4 ,RONG Rong 1,3
                                                                          1
                                                              1
       (1. School of Pharmacy,Shandong University of TCM,Jinan 250355,China;2. Experimental Center,
        Shandong University of TCM,Jinan 250355,China;3. Shandong Provincial Collaborative Innovation Center
        for Antiviral Traditional Chinese Medicine,Jinan 250355,China;4. Shandong Provincial Engineering Research
        Center for Antiviral Traditional Chinese Medicine,Jinan 250355,China)
        ABSTRACT    OBJECTIVE:To study the effects of Mahuang xixin fuzi decoction on Toll-like receptors (TLRs) response and
        cytochrome C oxidase (Cyt-CO)-mediated apoptosis regulation in mice with  influenza disease of kidney-yang deficiency.
        METHODS:Totally 48 male Balb/c mice were randomly divided into normal group(n=12)and modeling group(n=36). The
        modeling group was intraperitoneally injected with estradiol benzoate solution(8 mg/kg)and intranasally injected with influenza
        virus H1N1(20 μL/mice)to establish the influenza disease compound model of kidney-yang deficiency. After modeling,the
        mice were randomly divided into model group,positive drug group(Oseltamivir phosphate capsules,0.195 g/kg),Mahuang xixin
        fuzi decoction group (1.802 g/kg,by crude drug),with 12 mice in each group. Each group was given relevant medicine
                                                           intragastrically,normal group and model group were given
           Δ 基 金 项 目 :国 家 自 然 科 学 基 金 资 助 项 目(No.81873220 ,
                                                           corresponding volume of normal saline intragastrically 20
        No.81774167);山东省重大科技创新工程项目(No.2018CXGC1307);
                                                           mL/kg,once a day,for consecutive 6 days. During admi-
        山东省重点研发计划项目(No.2020CXGC010505)
                                                           nistration,body weight and anal temperature of mice were
           *硕士研究生。研究方向:中药及复方活性成分与质量控制。E-
                                                           measured daily;the percentage of initial body weight was
        mail:xsy407861520@163.com
           # 通信作者:教授,博士生导师,博士。研究方向:中药及复方活                  calculated. After last medication,the organ (spleen,thymus
        性成分与质量控制。E-mail:rosierong@163.com                  and lung) indexes were calculated;the pathological changes


        中国药房    2021年第32卷第6期                                               China Pharmacy 2021 Vol. 32 No. 6  ·669 ·
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