环氧化酶-2与氧化应激在急性肝损伤中的作用

The effect of cyclooxygenase-2 and oxidative stress in acute hepatic injury

目的 :研究环氧化酶 2 (COX 2 )在急性肝损伤中的表达 ,探讨COX 2与氧化应激在急性肝损伤中的作用。 方法 :将 3 0只Wistar大鼠随机分为三组 ,正常组 10只 ;对照组 10只 ,腹腔注射CCl4原液 1ml/kg ;实验组 10只 ,腹腔注射CCl4原液 1ml/kg、2h后给予 80mg/kg塞来昔布 (Celecoxib)灌胃。 结果 :血清学检测结果显示 ,对照组和实验组大鼠血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)和细菌内毒素 (LPS)均较正常组大鼠显著增高(P <0 .0 5 ) ,对照组与实验组大鼠血清ALT、AST和LPS水平差异显著 (P <0 .0 5 )。对照组和实验组大鼠肝匀浆一氧化氮 (NO)、丙二醛 (MDA)均较正常组大鼠明显增高 (P <0 .0 5 ) ,对照组与实验组大鼠血清NO和MDA水平差异显著 (P <0 .0 5 )。H E染色光镜下示对照组和实验组大鼠大量肝细胞肿胀、空泡变性和脂肪变性 ,部分肝细胞坏死。免疫组化结果显示COX 2在正常肝组织无表达 ,实验组大鼠较对照组大鼠COX 2表达明显增高 (P <0 .0 5 )。 结论 :急性肝损伤后 ,内毒素刺激COX 2表达 ,氧化应激反应加剧 ,COX 2表达和NO水平增高可能是机体对抗损伤的一种保护性机制。

Objectives:To study the expression of cyclooxygenase 2(COX 2) in acute hepatic injury and the relationship between COX 2 and oxidative stress. Methods:Thirty Wistar rats were divided into three groups: normal group: 10 rats, control group: 10 rats ip injection of 1 ml/g of CCl 4, model groups: 10 rats ip injection of 1 ml/kg of CCl 4 and after two hours ig of 80 mg/kg of Celecoxib. Results:Levels of serum ALT,AST and LPS in control rats were higher than normal rats. The indices were different significantly between control rats and model rats( P <0.05). The levels of liver homogenate NO and MDA in control rats and model rats were higher than normal rats, the difference between control rats and model rats were significant statistically ( P <0.05). H E stain showed hepatic cell swelling, vacuolation and steatosis in control and model rats. Immunohistochemical stain showed that the expression of COX 2 in model rats were higher than control rats. Conclusions:After acute hepatic injury, endotoxin induced the expression of COX 2 oxidative stress, which enhanced hepatic injury. The increased expression of COX 2 and NO might act as a protective role.