5-脂氧合酶在急性肝衰竭大鼠中的表达变化及意义  

The expression and the role of 5-lipoxygenase in rats of acute liver failure

作　　者：李璐[1] 马春华[1] 李珊珊[1] 张丹丹[1] 丁美[1] 陈煜[1] 

机构地区：[1]首都医科大学附属北京佑安医院人工肝中心,100069

出　　处：《北京医学》2013年第12期1007-1010,I0001,共5页Beijing Medical Journal

基　　金："十二五"国家科技重大专项(2012ZX10004-9 04;2012ZX10002-004;2013ZX10002-002);北京市卫生系统高层次卫生技术人才培养计划(2013-3-071);北京市卫生局"十百千"卫生人才专项

摘　　要：目的探讨5-脂氧合酶(5-lipoxygenase,5-LO)及其产物白三烯B4(Leukotriene B4,LTB4)在急性肝衰竭大鼠模型中的变化及其在肝脏炎性损伤中的作用。方法30只成年雄性Wistar品系大鼠分为实验对照组(6只)和肝衰竭模型组(24只)。通过腹腔注射D-氨基半乳糖及脂多糖建立大鼠急性肝衰竭模型,动态观察4、8、16、24 h各时间点大鼠肝组织的病理变化以及血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(T-BIL)的变化。荧光定量PCR测量肝组织5-LO mRNA变化,免疫组化法及蛋白质印迹法检测5-LO蛋白表达,ELISA试剂盒检测肝组织LTB4含量。结果联合腹腔注射D-氨基半乳糖/脂多糖后,血清中ALT、AST及T-BIL逐渐升高,24 h时达高峰,ALT(3992.6±290.7)U/L、AST(10 114.7±1 014.2)U/L,T-BIL(32.9±2.0)μmmol/L,与对照组比较差异有统计学意义(P<0.01)。24 h病理改变表现为肝细胞坏死、肝索解离,小叶及汇管区大量炎性细胞浸润。5-LO mRNA表达于造模后升高,8 h表达最高;与对照组比较,肝衰竭4、8、16 h的表达差异有统计学意义(P<0.01)。造模后肝组织5-LO表达呈持续升高,24 h表达最高。LTB4含量与5-LO变化趋势相同,于造模后24 h浓度最高,为(355.4±22.2)pg/ml。结论5-LO及其产物LTB4参与急性肝衰竭的病理生理过程,并发挥重要的作用。Objective To investigate the expression and the role of 5-LO, LTB4 in the rats with acute liver failure （ALF）. Methods Thirty Wistar rats were divided into 2 groups. Control group （n=6） was given intraperitoneal injection of 0.9% NaC1 2 ml. Model group （n=24） was given joint injection of D-GaIN and LPS according to their weight. Six rats were randomly picked respectively after 4,8,16,24 h since modeling and the changes of patholoy and liver function of each rat were dynamic viewed. RT-PCR was used to detect the 5-LO mRNA content variation, WB and IHC-P method were used to detect the 5-LO protein content variation in the reserved hepatic tissues. The ELISA kit was used to detect the content of LTB4 in the liver tissue. Results After administrating D-GalN/LPS, the levels of aminotransferases were increased sig- nificantly （P 〈 0.01） and peaked at 24 h[ALT （3 992.6±290.7）U/L, AST（10 114.7±I 014.2）U/L, T-BIL（32.9±2.0）μmmol/L], and pathological change was in accordance with that of ALF. The expression of 5-LO mRNA in the liver tissue was gradu- ally increased with the development of inflammation and peaked at 8 h after the injection with D-GalN/LPS（P 〈 0.01）, then decreased. While the expression of 5-LO protein was continuous increased and peaked at 24 h after modeling. And the level of LTB4 was positively related with the expression of 5-LO in the process of ALF. Conclusion 5-LO and LTB4 participate and play important roles in the pathological processes of ALF.

关 键 词：急性肝衰竭 5-脂氧合酶 白三烯B4 

分 类 号：R575.3[医药卫生—消化系统]