【作者】 肖佳； 邢飞跃； George L.Tipoe；

【Author】 XIAO Jia;XING Feiyue;George L. Tipoe;Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University;Department of Anatomy, Li Ka Shing Faculty of Medicine,The University of Hong Kong;

【机构】 暨南大学生命科学技术学院免疫生物学系； 香港大学李嘉诚医学院解剖学系；

【摘要】 环氧合酶-1(COX-1)是COX家族中组成性表达的成员。为探讨COX-1在急性肝损伤中的作用和机制,通过注射四氯化碳(CCl4)诱导野生型或COX-1敲除小鼠的急性肝损伤,研究各种损伤表征的变化。结果表明,完全或部分敲除COX-1基因、使用药物抑制COX-1酶活性均可恶化四氯化碳造成的急性肝损伤,主要表现在:(1)恶化的肝脏组织学和血清中转氨酶的变化;(2)通过CYP2E1介导的氧化压力的恶化;(3)升高的肝脏炎症反应;(4)恶化的肝脏凋亡反应。研究表明,肝脏中COX-1的基本表达水平对于肝脏抵御化学急性损伤非常重要。更多还原

【Abstract】 Cyclooxygenase-1(COX-1) is the constitutive form of the COX enzyme family which produces bioactive lipids called prostanoids. Although the role of COX-2 in liver diseases has been studied, little is known about the function of COX-1 in liver injury. We aimed to find out the role and mechanism of COX-1 in acute liver injury. Carbon tetrachloride(CCl4) was administered in to induce acute liver injury in wild-type or COX-1 deficient mice. Both genetic(partially or completely) deletion of COX-1 expression and pharmacological inhibition of COX-1 activity in mice exacerbated acute liver injury induced by CCl4, revealing that:(1) histopathological changes and increased serum levels of aminotransferases;(2) oxidative stress in the liver partly through the action of cytochrome P450 2E1-dependent pathway;(3) enhanced inflammatory and chemoattractive responses with increased number of activated macrophages;(4) aggravated apoptosis through both intrinsic and extrinsic apoptotic pathways. In conclusion, basal expression of COX-1 is essential for the protection of liver in chemical-induced hepatotoxicity and hepatic homeostasis maintenance.更多还原