滨蒿内酯对四氯化碳致小鼠急性肝损伤的保护作用研究
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篇名: 滨蒿内酯对四氯化碳致小鼠急性肝损伤的保护作用研究
TITLE: Study on Protective Effects of Scoparone on Acute Liver Injury Induced by CCl 4 in Mice
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,120mg/kg)和滨蒿内酯高、低剂量组(60、30mg/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7d。末次给药结束2h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(1mL/100g)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-κBp65、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-κBp65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-κBp65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。
ABSTRACT: OBJECTIVE:To study the protec tive effects of scoparone on acute liver injury induced by CCl 4 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,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-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 CCl 4-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.
期刊: 2021年第32卷第02期
作者: 彭静,陈曦
AUTHORS: PENG Jing ,CHEN Xi
关键字: 滨蒿内酯;急性肝损伤;NF-κB通路;氧化应激;炎症;小鼠
KEYWORDS: Scoparone;Acute liver injury ;NF-κB pathway;Oxidative stress ;Inflammation;Mice
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