环氧合酶2抑制剂在胆固醇结石形成中的作用

目的　探讨选择性环氧合酶 2 (COX 2 )抑制剂塞莱昔布 (celexibo)在家兔实验性胆固醇结石形成中的作用。方法　普通家兔 30只平均分为 3组 :成石组饲以高胆固醇饲料 ,实验组在高胆固醇饲料基础上按每天 10mg/kg体重加饲塞莱昔布 ,空白组饲以普通饲料。 7周后 ,观察各组胆囊胆汁结晶情况、胆囊上皮黏膜炎症情况及COX 2含量。结果　实验组比成石组形成胆固醇结晶机会明显减少 (9/ 10、2 / 10 ,χ2 =9 988,P <0 0 5 ) ;成石组比空白组胆囊黏膜炎症程度明显升高 (U =2 3,W =6 8,P <0 0 5 ) ,实验组与成石组相比 ,炎症程度显著降低 (U =18,W =6 3,P <0 0 1)。成石组胆囊黏膜COX 2表达量明显高于空白组 (0 0 5 5± 0 0 0 6、0 0 17± 0 0 0 3,P <0 0 0 1) ,实验组比成石组COX 2表达量明显降低 (0 16 9± 0 0 0 1、0 0 5 5± 0 0 0 6 ,P <0 0 0 1)。结论　胆固醇结石形成可能包含炎症机制 ,COX 2参与胆固醇结石的形成过程 ,且COX 2抑制剂可以抑制胆固醇结石的形成。

The impact of selective cycloxygenase-2 inhibitor celexibo on the formation of cholesterol gallstone

OBJECTIVE: To determine the effects of specific cyclooxygenase-2 (COX-2) inhibitor celexibo on the formation of gallstone in rabbits by comparing both the mucosa damage and the risk of gallstone formation. METHODS: 30 rabbits were equally divided into three groups: gallstone group (induced by high cholesterol diet HCD), celexibo group (treated with celexibo 10 mg.kg(-1).day(-1) in addition to HCD) and control group (fed with formal diet). After 7 weeks, bile was obtained for observing gallstone formation, and the morphologic changes of the mucosa were assessed under microscopy. The level of COX-2 in gallbladder mucosa in each group was estimated with immunohistochemical assay. RESULTS: Celexibo group had lower risk to get gallstones than gallstone group (2/10 vs 9/10, P < 0.05). The degree of mucosa inflammation and level of COX-2 expression were significantly higher in gallstone group than in the other two groups (0.055 +/- 0.006 vs 0.017 +/- 0.003, P < 0.001; 0.055 +/- 0.006 vs 0.169 +/- 0.001, P < 0.001). CONCLUSIONS: Specific COX-2 inhibitor celexibo can decrease the risk of gallstone formation. COX-2 is highly expressed in gallbladder mucosa of gallstone, which suggests that there is certain inflammatory mechanism in the cholesterol gallstone formation.