天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (7): 694-698.doi: 10.11958/20203056

• 实验研究 • 上一篇    下一篇

大麻二酚通过激活PPAR-γ减轻四氯化碳所致小鼠急性肝损伤

舒远辉，马润，谢娜，李垚，王豫萍   

  1. 1贵州医科大学医学检验学院（邮编550004）；2贵州医科大学附属医院临床检验中心
  • 收稿日期:2020-11-05 修回日期:2021-03-06 出版日期:2021-07-15 发布日期:2021-07-12
  • 通讯作者: 1500776978@qq.com E-mail:1500776978@qq.com
  • 作者简介:舒远辉（1990），男，硕士在读，主要从事肝炎与肝纤维化相关的基础研究。E-mail：565164259@qq.com
  • 基金资助:
    国家自然科学基金资助项目（81860118）

Cannabidiol reduces CCl4-induced acute liver injury in mice by activating PPAR-γ

SHU Yuan-hui, MA Run, XIE Na, LI Yao, WANG Yu-ping   

  1. 1 School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550004, China; 2 Clinical Laboratory Center, the Affiliated Hospital of Guizhou Medical University
  • Received:2020-11-05 Revised:2021-03-06 Published:2021-07-15 Online:2021-07-12

PDF (PC)

3842

摘要： 目的　探究大麻二酚（CBD）对四氯化碳（CCl4）诱导小鼠急性肝损伤的防治作用及机制。方法　42只6~8周龄C57BL/6J雄性小鼠随机分为对照组（9只）、模型组（9只）、CBD对照组（9只）、还原型谷胱甘肽（GSH）干预组（6只）、CBD干预组（9只），其中CBD对照组、GSH干预组、CBD干预组分别腹腔注射CBD 5 mg/kg、GSH 200 mg/kg、CBD 5 mg/kg，对照组、模型组注射相同剂量的生理盐水。2 h后模型组、GSH干预组、CBD干预组分别腹腔注射含20% CCl4橄榄油5 mL/kg建立急性肝损伤模型，24 h后取血清检测丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平；HE染色观察小鼠肝组织病理变化；肝组织匀浆检测超氧化物歧化酶（SOD）、丙二醛（MDA）和GSH水平；Western blot检测肝组织过氧化物增殖物激活受体-γ（PPAR-γ）、环氧合酶-2（COX-2）蛋白的表达。结果　与对照组比较，模型组细胞损伤坏死严重，ALT、AST、MDA水平及COX-2蛋白表达水平明显升高，SOD、GSH水平及PPAR-γ蛋白表达水平明显降低（均P＜0.05）；与模型组比较，GSH干预组、CBD干预组肝脏病理损伤明显减轻，ALT、AST、MDA水平及COX-2蛋白表达水平明显降低，SOD、GSH水平及PPAR-γ蛋白表达水平明显升高（均P＜0.05）。结论　CBD对CCl4所致小鼠急性肝损伤有一定的预防作用，其机制可能与激活PPAR-γ抑制COX-2的表达，发挥抗炎抗氧化作用有关。

关键词: 大麻二酚, 四氯化碳, PPARγ, 环氧化酶2, 化学性与药物性肝损伤, 氧化性应激, 急性肝损伤

Abstract: Objective　To explore the prevention and mechanism of cannabidiol (CBD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. Methods　Forty-two C57BL/6J male mice aged 6-8 weeks were divided into 5 groups according to the random number table method: control group (n=9), model group (n=9), CBD control group (n=9), glutathione (GSH) intervention group (n=6) and CBD intervention group (n=9). The CBD control group, GSH intervention group and CBD intervention group were intraperitoneally injected with CBD 5 mg/kg, GSH 200 mg/kg and CBD 5 mg/kg respectively. The control group and model group were injected with the same dose of normal saline. Two hours later, the model group, GSH intervention group and CBD intervention group were intraperitoneally injected with 20% CCl4 olive oil 5 mL/kg to establish the acute liver injury model. After 24 h, the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. HE staining was used to observe the pathological changes of mouse liver tissue. The activities of superoxide dismutase (SOD), malondialdehyde (MDA) and GSH were detected by liver tissue homogenate method. PPAR-γ and COX-2 protein expression levels in liver tissue were detected by Western blot assay. Results　Compared with the control group, the model group had severe cell damage and necrosis, ALT, AST, MDA and COX-2 levels were significantly increased in the model group (P＜0.05), and the SOD, GSH and PPAR-γ levels were significantly reduced (P＜0.05). Compared with the model group, liver pathological damages significantly reduced in the GSH intervention group and CBD intervention group, and ALT, AST, MDA and COX-2 levels were significantly reduced (P＜0.05), whereas SOD, GSH and PPAR-γ levels were significantly increased (P＜0.05). Conclusion　CBD can prevent CCl4 induced the acute liver injury in mice, which may be related to the activation of PPAR-γ, the inhibition of COX-2 expression and anti-inflammatory and antioxidant effects.

Key words: cannabidiol, carbon tetrachloride, PPAR gammacy, clooxygenase 2, chemical and drug induced liver injury, oxidative stress, acute liver injury