癌变·畸变·突变 ›› 2023, Vol. 35 ›› Issue (2): 95-101.doi: 10.3969/j.issn.1004-616x.2023.02.003

• 论著 • 上一篇    

明日叶查尔酮对小鼠急性酒精性肝损伤的保护作用

陈双1, 彭中芮1, 吴桢雯1, 郭东北1, 孙美君2, 李蕾1   

  1. 1. 厦门大学公共卫生学院分子疫苗学和分子诊断学国家重点实验室, 福建 厦门 361102;
    2. 临沂市疾病预防控制中心, 山东 临沂 273399
  • 收稿日期:2022-11-24 修回日期:2022-12-23 发布日期:2023-04-13
  • 通讯作者: 孙美君;李蕾
  • 作者简介:陈双,E-mail:1004303073@qq.com。
  • 基金资助:
    厦门大学大学生创新创业训练项目(2020Y0797)

Protective effects of angelica keiskei chalcones on acute alcoholic liver injury in mice

CHEN Shuang1, PENG Zhongrui1, WU Zhenwen1, GUO Dongbei1, SUN Meijun2, LI Lei1   

  1. 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Public Health School, Xiamen University, Xiamen 361102, Fujian;
    2. Linyi Center for Disease Control and Prevention, Linyi 273399, Shandong, China
  • Received:2022-11-24 Revised:2022-12-23 Published:2023-04-13

摘要: 目的:研究明日叶查尔酮(AC)对小鼠急性酒精性肝损伤的保护作用。方法:将60只BALB/c雄性小鼠随机分为正常对照组,酒精模型组,AC 低(5 mg/kg)、中(15 mg/kg)、高(30 mg/kg)剂量组,每组12只。灌胃给予受试物,体积为10 μL/g,每天1次,连续30 d,正常对照组与酒精模型组给予等体积生理盐水。末次给药12 h后,除正常对照组外,其余4组小鼠均一次性灌胃50%酒精,灌胃量为 12 mL/kg。灌胃 12 h 后,眼球取血,分离血清,分别测定肝脏损伤指标谷丙转氨酶(ALT)、谷草转氨酶(AST),脂质代谢指标低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、总胆固醇(TC)、甘油三酯(TG),氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)和细胞凋亡相关指标,并进行肝脏组织病理学观察。结果:与正常对照组相比,酒精模型组小鼠肝脏系数显著升高(P<0.05),肝脏出现明显的炎性细胞浸润;血清转氨酶活性、TC、TG和LDL-C含量均显著升高(P<0.05),而HDL-C水平明显降低(P<0.05);血清SOD和GSH-Px活性明显降低(P<0.05),MDA含量显著升高(P<0.05);肝细胞凋亡率明显升高(P<0.05)。与酒精模型组相比,中、高剂量AC组小鼠的肝脏系数显著降低(P<0.05),肝细胞炎性细胞浸润明显改善;血清转氨酶活性、TC、TG和LDL-C含量均显著降低(P<0.05),而HDL-C水平明显升高(P<0.05);血清SOD和GSH-Px活性明显升高(P<0.05),MDA含量显著降低(P<0.05);肝细胞凋亡率明显降低(P<0.05)。结论:AC对酒精引发的急性肝损伤具有良好的防护作用,其机制可能与抑制脂质代谢紊乱,减轻氧化损伤,抑制细胞凋亡有关。

关键词: 明日叶查尔酮, 酒精性肝损伤, 脂质代谢, 氧化损伤, 细胞凋亡

Abstract: OBJECTIVE: The present study aimed to investigate protective effects of angelica keiskei chaclones (AC) on acute alcohol liver injury in mice. METHODS:Sixty healthy mice were divided randomly into five groups (12 mice per group): normal control,alcohol model,and low-(5 mg/kg),medium-(15 mg/ kg) and high-dose (30 mg/kg) groups. AC was intragastrically administrated with a volume of 10 μL/g once a day for 30 days. Mice in the normal control and alcohol model groups were given equal volumes of saline. Twelve hours after the last administration,all mice except those in the normal control group were given 50% alcohol by gavage at a dose of 12 mL/kg. After 12 hours, all mice were sacrificed. Blood samples were collected from eyeballs and serum was isolated. Indicators of liver injury in glutamic pyruvic transaminase (ALT) and glutamic oxaloacetic transaminase (AST), lipid metabolism of low-density lipoprotein cholesterol (LDL-C)、 high-density lipoprotein cholesterol (HDL-C)、 total cholesterol(TC)and triglyceride (TG), oxidative stress of superoxide dismutase (SOD)、 malondialdehyde (MDA)and glutathione peroxidase (GSH-Px), and cell apoptosis were evaluated. Liver histopathology was examined as well. RESULTS:Compared with the normal control group, the liver indices in the alcohol control group were significantly increased with obvious inflammatory cell infiltration (P<0.05). Their serum transaminase activity and contents of serum TC, T and LDL-C were obviously increased and HDL was significantly reduced (P<0.05). Their activities of SOD and GSH-Px were significantly decreased, and the content of MDA was increased obviously (P<0.05). Their apoptosis rates of hepatocytes were obviously increased (P<0.05). Compared with the alcohol model group,the liver indices for the medium-and high-dose AC groups were significantly decreased (P<0.05), and inflammatory cell infiltrations were obviously reduced. Their serum transaminase activities and contents of serum TC, TG and LDL-C were significantly decreased (P<0.05). Their activities of SOD and GSH-Px were effectively increased, and the contents of MDA were reduced obviously (P<0.05). Their apoptosis rates of hepatocytes were also significantly lower than the alcohol model group (P<0.05). CONCLUSION:AC exhibited protective effects on acute alcoholic liver injury. A mechanism may be related to reduction of lipid peroxidation,modulation of lipid metabolism and inhibition of hepatocyte apoptosis.

Key words: angelica keiskei chaclones, alcoholic liver injury, lipid metabolism, oxidative damage, apoptosis

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