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滨蒿内酯对四氯化碳致小鼠急性肝损伤的保护作用研究                                                              Δ


        彭 静 ,陈 曦(1.乐山职业技术学院中医教研室,四川 乐山 614000;2.乐山市市中区人民医院中医科,四
              1*
                        2
        川 乐山 614000)

        中图分类号 R965          文献标志码 A          文章编号 1001-0408(2021)02-0231-05
        DOI  10.6039/j.issn.1001-0408.2021.02.18

        摘  要   目的:研究滨蒿内酯对四氯化碳(CCl4 )致小鼠急性肝损伤的保护作用及潜在分子机制。方法:将50只雄性昆明种小鼠随
        机分为正常对照组、模型组、水飞蓟素组(阳性对照,120 mg/kg)和滨蒿内酯高、低剂量组(60、30 mg/kg),每组10只。各给药组小
        鼠均灌胃相应药物,正常对照组和模型组小鼠灌胃等体积0.5%羧甲基纤维素钠溶液,每日1次,连续给药7 d。末次给药结束2 h
        后,除正常对照组小鼠腹腔注射等体积橄榄油外,其余组小鼠均一次性腹腔注射0.1%CCl4橄榄油溶液(1 mL/100 g)以建立急性肝
        损伤模型。采用苏木精-伊红(HE)染色法观察小鼠肝组织病理性改变;采用酶联免疫吸附法检测小鼠血清中天冬氨酸转氨酶
       (AST)、丙氨酸转氨酶(ALT)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性和白细胞介素 1β(IL-1β)、IL-6、肿瘤坏死因子α
       (TNF-α)、丙二醛(MDA)的含量;采用蛋白免疫印迹法检测小鼠肝组织中核因子κB(NF-κB)通路相关蛋白[NF-κB p65、核因子κ
        Bα激酶抑制蛋白(IκBα)]的磷酸化水平。结果:与正常对照组比较,模型组小鼠血清中AST、ALT活性和MDA、IL-1β、IL-6、TNF-α
        含量均显著升高,SOD、CAT活性均显著降低(P<0.05);肝组织出现明显的病理性改变,且肝组织中NF-κB p65和IκBα蛋白的磷酸化
        水平均显著升高(P<0.05)。与模型组比较,水飞蓟素组和滨蒿内酯高、低剂量组小鼠血清中相关因子活性或含量水平均显著逆转
       (P<0.05);肝组织病理性改变程度明显减轻,且肝组织中NF-κB p65和IκBα蛋白的磷酸化水平均显著降低(P<0.05)。结论:滨蒿内
        酯对CCl4所致小鼠急性肝损伤具有保护作用,该作用与降低氧化应激水平以及阻断NF-κB通路的活化、进而抑制炎症反应有关。
        关键词 滨蒿内酯;急性肝损伤;NF-κB通路;氧化应激;炎症;小鼠

        Study on Protective Effects of Scoparone on Acute Liver Injury Induced by CCl4 in Mice
                            2
        PENG Jing ,CHEN Xi(1. Teaching and Research Section of Traditional Chinese Medicine,Leshan Vocational
                  1
        and Technical College,Sichuan Leshan 614000,China;2. Dept. of Traditional Chinese Medicine,Leshan
        Shizhong District People’s Hospital,Sichuan Leshan 614000,China)

        ABSTRACT    OBJECTIVE:To study the protective effects of scoparone on acute liver injury induced by CCl4 in mice and its
        potential molecular mechanism. METHODS:Fifty male Kunming mice were randomly divided into normal control group,model
        group,silymarin group(positive control,120 mg/kg),scoparone high-dose and low-dose groups(60,30 mg/kg),with 10 mice
        in each group. Administration groups were given relevant medicine intragastrically. Normal control group and model group were
        given constant volume of 0.5% sodium carboxymethyl cellulose solution,once a day,for 7 days. Two hours after last medication,
        except normal control group was intraperitoneally injected constant volume of olive oil,other groups were intraperitoneally injected
        0.1% CCl4 olive oil solution(10 mL/kg)at one time to establish the acute liver injury model. The pathological changes of liver
        tissues in mice were observed by HE staining;the activity of AST,ALT,SOD and CAT and the contents of IL-1β,IL-6,TNF-α
        and MDA in serum were measured by ELISA;the phosphorylation of nuclear factor κB(NF-κB)pathway related proteins(NF-κB
        p65,I κ B α)in liver tissue were detected by Western blotting assay. RESULTS:Compared with normal control group,serum
        activities of AST and ALT,the contents of MDA,IL-1 β ,IL-6 and TNF-α were significantly increased in model group,the
        activities of SOD and CAT were decreased significantly(P<0.05);obvious pathological changes were observed in liver tissues;
        phosphorylation levels of NF-κB p65 and IκBα protein in liver tissues were significantly increased(P<0.05). Compared with
        model group,the activities or contens of related factors in serum of mice were significantly reversed in silymarin group and
        scoparone high-dose and low-dose groups (P<0.05);the pathological changes of liver tissues were significantly reduced;the
        phosphorylation levels of NF-κB p65 and IκBα protein in liver tissues were significantly reduced(P<0.05). CONCLUSIONS:
        Scoparone has a protective effect on CCl4-induced acute liver injury in mice,which is related to reducing oxidative stress levels and
        blocking the activation of NF-κB pathway,thereby inhibiting inflammatory response.
        KEYWORDS    Scoparone;Acute liver injury;NF-κB pathway;Oxidative stress;Inflammation;Mice


                                                               滨 蒿 内 酯 为 传 统 中 药 滨 蒿 Artemisia scoparia
           Δ 基金项目:乐山市重点科技计划项目(No.19SZD207)
           *副教授,硕士。研究方向:中医药治疗慢性病。电话:0833-                  Waldst. et Kit.、茵陈蒿 Artemisia capillaries Thunb.和石
        2152787。E-mail:pengjingls@126.com                  斛 Dendrobium Sw.中的有效成分,又名七叶内酯二甲


        中国药房    2021年第32卷第2期                                               China Pharmacy 2021 Vol. 32 No. 2  ·231 ·
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