彭静 陈曦

摘 要 目的：研究濱蒿内酯对四氯化碳（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。

关键词 滨蒿内酯;急性肝损伤;NF-κB通路;氧化应激;炎症;小鼠

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， 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 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

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

滨蒿内酯为传统中药滨蒿Artemisia scoparia Waldst. et Kit.、茵陈蒿Artemisia capillaries Thunb.和石斛Dendrobium Sw.中的有效成分，又名七叶内酯二甲醚、6，7-二甲氧基香豆素、东喘宁、蒿属香豆精等，具有平喘止咳、抗辐射、抑制免疫、舒张血管、调血脂、消炎镇痛和降血压等功效，临床上主要用于支气管哮喘、心绞痛及冠心病等症的治疗[1]。近年来，滨蒿内酯在非酒精性脂肪性肝病的治疗中表现出较好的效果，具有减轻肝组织脂肪性改变等作用，逐渐得到人们的重视[2]。……