滨蒿内酯对四氯化碳致小鼠急性肝损伤的保护作用研究  

Study on Protective Effects of Scoparone on Acute Liver Injury Induced by CCl4 in Mice

作　　者：彭静[1] 陈曦[2] PENG Jing;CHEN Xi(Teaching and Research Section of Traditional Chinese Medicine,Leshan Vocational and Technical College,Sichuan Leshan 614000,China;Dept.of Traditional Chinese Medicine,Leshan Shizhong District People’s Hospital,Sichuan Leshan 614000,China)

机构地区：[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,四川乐山614000

出　　处：《中国药房》2021年第2期231-235,共5页China Pharmacy

基　　金：乐山市重点科技计划项目(No.19SZD207)。

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κBα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。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 injected0.1%CCl4 olive oil solution(10 m L/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-αand MDA in serum were measured by ELISA;the phosphorylation of nuclear factorκB(NF-κB)pathway related proteins(NF-κB p65,IκBα)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-1β,IL-6 and TNF-αwere 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 IκBαprotein 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 IκBαprotein 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 stre

关 键 词：滨蒿内酯 急性肝损伤 NF-ΚB通路 氧化应激 炎症 小鼠 

分 类 号：R965[医药卫生—药理学]