选择性环氧合酶-2抑制剂对大鼠酒精性肝损伤的保护作用

Protective effect of selective cyclooxygenase-2 inhibitor on alcohol-induced liver injury in rats

目的 了解环氧合酶-2(COX-2)在大鼠酒精性肝损伤中的作用机理,探讨选择性COX-2抑制剂对大鼠酒精性肝损伤的作用。 方法 58只Wistar大鼠,随机分为3组,对照组(n=10)用玉米油+葡萄糖;模型组(n=24)用酒精+玉米油;处理组(n=24)在模型组基础上给予选择性COX-2抑制剂塞莱昔布。23 d后处死大鼠,测定大鼠血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血浆和肝组织匀浆谷胱甘肽-S转移酶(GST)活性以及肝组织匀浆6-酮-前列腺素F1α(6-k-PGF1 α)和血栓素B2(TXB2)含量。光镜和电镜观察肝组织细胞及亚细胞结构的改变;免疫印迹法检测各组大鼠肝组织中COX-2蛋白的表达。 结果 模型组肝细胞损伤明显,处理组较轻。模型组大鼠血清AST、ALT、肝组织TXB 2和血浆GST比对照组明显升高,t=4.552～2.294,P<0.01～0.05,肝组织GST则模型组较对照组明显降低,t=8.856,P<0.01。与模型组相比,处理组大鼠血清AST、肝组织TXB2明显降低,t=4.305和2.799,P<0.01,肝组织GST明显升高,t=10.1 34,P<0.001,而血清ALT降低和血浆GST升高则不明显(P>0.05)。肝组织6-k-PGF1α的变化模型组较对照组降低,t=2.284,P<0.05,处理组较模型组降低,但P>0.05。Western blot显示,肝组织中COX-2表达模型组较对照组明显升高(t=4.067,P<0.01)。

Objective To investigate the effect of selective cyclooxygenase-2 (COX-2) inhibitor on alcohol-induced liver injury in rats. Methods 58 male Wistar rats were randomly divided into three groups: control group treated with dextrose and corn oil, model group with ethanol and corn oil, treatment group with corn oil and ethanol plus a selective COX-2 inhibitor celecoxib. All treatments were injected into stomach through intragastric tubes. Liver samples were analyzed for histopathology with light microscope (LM) and transmission electron microscope (TEM), and the expression of COX-2 with western blotting. Levels of aspartate aminotransferase (AST) and alanine ami-notransferase (ALT) in serum, levels of 6-Keto-prostaglandin F1 alpha (6-k-PGF1α) and thromboxane B2 (TXB2) in liver, and activity of glutathione s-transferase (GST) both in liver tissue and in plasma were measured. Results LM and TEM indicated hepatocytes were injured obviously in the model group and slightly in the treatment group. The levels of AST and ALT in serum, TXB2 in liver and the activity of GST in plasma increased significantly in the model group (t ≥ 2.294, P < 0.05), but the activity of GST in liver decreased significantly (t = 8.856, P < 0.01) compared with those in the control group. To compare with the model group, the levels of AST and TXB2 decreased significantly (t = 4.305, P < 0.01; t = 2.799, P < 0.01), meanwhile the activity of GST increased significantly (t = 10.134, P < 0.01) in the treatment group. COX-2 expression in liver by western blotting increased significantly in the model group, compared with the control group (t = 4.067, P < 0.01) and the treatment group (t = 2.251, P < 0.05). Exceptionally, the level of 6-k-PGF1α decreased significantly (t = 2.284, P < 0.05) in the model group. Conclusions COX-2 has involved in the alcohol-induced liver injury, and its inhibitor can diminish alcohol-induced liver injury in rats through decreasing TXB2 level.