牛磺熊去氧胆酸对脂肪肝缺血再灌注损伤影响的实验研究  

Experimental study of the effect of taurine-conjugated ursodeoxycholic acid for ischemia reperfusion injury in fatty liver of rats

作　　者：邢雨[1] 蔡金贞[2] 张建军[1,2] 李世朋[1] 王政禄[2] 王玉亮[2,3] 

机构地区：[1]天津医科大学一中心临床学院,天津300192 [2]天津市第一中心医院器官移植中心,天津300192 [3]卫生部危重病急救医学重点实验室,天津300384

出　　处：《中国临床药理学杂志》2014年第11期1017-1019,1029,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家高技术研究发展计划(863)基金资助项目(2012AA021001);国家自然科学基金资助项目(81170443);公益性行业科研专项基金资助项目(201302009);天津市卫生局科技基金资助项目(2011KZ31)

摘　　要：目的探讨牛磺熊去氧胆酸(TUDCA)对自体肝移植大鼠脂肪肝缺血再灌注损伤的保护作用。方法 Wistar大鼠随机分为对照组、模型组和TUDCA组,用脂肪肝大鼠自体肝移植诱导缺血再灌注损伤模型,缺血后分别给予蛋白液和含10 mmol·L-1TUDCA的蛋白液,以1.5 m L·min-1的速度灌洗45 m L,于6,24 h后检测血清丙氨酸氨基转移酶(ALT)与血清天门冬氨酸氨基转移酶(AST)含量;肝组织中超氧化物歧化酶(SOD)含量;取肝组织做病理组织学检测;免疫组化方法检测肝组织中核因子活化B细胞κ轻链增强子(NF-κB)的活化程度。结果 TUDCA能降低大鼠血清中ALT、AST含量,并提高SOD的含量(P<0.05);TUDCA组中的肝细胞水肿及汇管区炎性细胞浸润轻于模型组;TUDCA组比模型组NF-κB表达明显减少(P<0.05)。结论 TUDCA通过减轻内质网应激和减少NF-κB表达,对脂肪肝大鼠IRI起到保护作用。Objective To explore the effect of taurine -conjugated ursodeoxycholic acid （ TUDCA ） intervention for reducing liver ischemia reperfusion injury in rats after liver autotransplantation.Methods Wist-ar rats were randomly divided into three groups：the control group, the TUDCA group and the model group.Liver autotransplantation for Wistar rat ischemia reperfusion injury （ IRI） model was established.After ische-mia were given protein solution and the protein solution containing the 10 mmol·L^-1 TUDCA 1.5 mL· min^-1 speed lavage 45 mL,at the time of the 6 h and 24 h after operation for determining serum levels of alanine aminotransferase （ ALT ） and aspartate aminotransferase （ AST ） .The activity of superoxide dismutase （ SOD） in liver tissue was determined.The pathological examination of liver was performed as well and detecting the expression of nuclear factor kappa-light-chain-enhancer of acti-vated B cells （ NF-κB） in liver tissue by immunohistochemical method.Results Compared with the model group, in the TUDCA group at any time points after operation, the serum levels of ALT,AST were lower and liver tissue SOD were higher（ P〈0.05）.The model group is to enhance the expression of NF-κB, the TUDCA group was eakened （P〈0.05） and the pathologic changes （ hepatocyte swelling and portal area inflammation cellinfiltration） were lessened.Conclusion TUDCA can reduce endoplasmic reticulum stress and reduc-tion expression of NF-κB, protective effect in liver ischemic reperfusion injury in fatty liver of rats.

关 键 词：牛磺熊去氧胆酸 脂肪肝 缺血再灌注损伤 核因子活化B细胞κ轻链增强子 

分 类 号：R575.5[医药卫生—消化系统] R285.5[医药卫生—内科学]