干扰花生四烯酸代谢的药物对实验性肝损伤的影响

EFFECTS OF THE COMPOUNDS INTERFERING WITH ARICHIDONIC ACID METABOLISM ON EXPERIMENTAL LIVER INJURY IN MICE

目的：研究干扰花生四烯酸（ＡＡ）代谢的药物对实验性肝损伤的影响，探讨ＡＡ代谢与肝损伤的关系。方法：选择四氯化碳（ＣＣｌ４）、醋氨酚、卡介苗加细菌脂多糖所致的小鼠肝损伤模型，以血清谷丙转氨酶（ＡＬＴ）、肝脏丙二醛（ＭＤＡ） 和谷胱甘肽（ＧＳＨ） 水平为观察生化指标，同时光镜下观察组织病理学改变。结果：影响ＡＡ代谢的磷脂酶Ａ２（ＰＬＡ２） 抑制剂氯喹，环氧酶（ＣＯ） 抑制剂阿司匹林，环氧酶及脂氧酶（ＬＯ）双酶抑制剂氟灭酸对上述三种实验性肝损伤均无明显影响。而脂氧酶抑制剂黄芩甙和白三烯（ＬＴｓ） 受体拮抗剂ＧＬ３ 对实验性肝损伤有明显的保护作用。结论：上述结果提示ＡＡ 代谢ＬＯ途径产物如ＬＴｓ 可能在肝损中起着重要作用。

AIM To investigate the effects of the compounds interfering with arichidonic acid (AA) metabolism, on the experimental liver injury,and to study the relationship between AA metabolism and liver injury.METHODS In the CCl 4, acetaminophen (APAP), BCG and lipopolysaccharide (LPS)-induced liver injury animal models, the levels of AL, MDA, GSH and the pathologic changes of liver tissues were observed and compared in animals treated with different compounds.RESULTS Baicalin,inhibitor of LO (Lipooxygenase LO) and GL 3,antagonist of LTs showed obvious protective effects against experimental liver injury, while chloroquine, inhibitor of phospholipases A 2(PLA 2), aspirin, inhibitor of (cyclooxygenase,CO), flufenamic acid, inhibitor of both CO and LO showed no liver protective effects.CONCLUTION Metabolites of LO pathway,such as (Leukotriens,LTs),may play an important role in liver injury development.