肝胆汁酸合成及转运异常在大鼠结肠炎性胆汁淤积发病中的作用

发布时间：2018-06-24 23:06

本文选题：溃疡性结肠炎 + 胆汁淤积　；参考：《中国临床药理学杂志》2017年18期

【摘要】：目的研究肝胆汁酸合成及转运异常在结肠炎性胆汁淤积发生中的作用及其机制。方法按照体重将Wistar雄性大鼠随机分成2组:正常组和模型组。模型组大鼠给予2,4,6-三硝基苯磺酸结肠灌注制备溃疡性结肠炎(UC)模型,正常组大鼠结肠给予0.9%Na Cl。考察动物的病变活动指数、病理组织评分及髓过氧化物酶活性;测定动物的血清碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、谷草转氨酶(AST)和谷丙转氨酶(ALT)含量;以液质联用技术测定肝总胆汁酸、脱氧胆酸及石胆酸含量;用免疫印迹技术测定肝中胆汁酸合成限速酶胆固醇7α羟化酶(Cyp7a1)及胆汁酸外排转运体多药耐药性相关蛋白2(Mrp2)的表达。结果与正常组比较,模型组病变活动指数、病理组织评分及髓过氧化物酶活性分别为4.51±1.49,(1.36±0.69)分和(0.40±0.07)U·mg~(-1),差异均有统计学意义(均P0.05),说明UC模型制备成功。模型组大鼠肝总胆汁酸及脱氧胆酸含量分别为(85.50±18.60)μmol·L~(-1)和(79.53±32.99)ng·g~(-1),血清ALP和GGT水平分别为(259.43±58.58),(1.50±0.68)U·L~(-1),与正常组比较差异均有统计学意义(均P0.05),提示模型组大鼠存在肝内胆汁淤积。与正常组相比,模型组大鼠肝Cyp7a1的表达灰度值为0.72±0.07;而转运体Mrp2的表达灰度值为0.66±0.04;与正常组比较差异均有统计学意义(均P0.05)。结论模型组大鼠存在明显的肝内胆汁淤积,其发生与肝胆汁酸合成增多及胆汁酸外排减少有关。
[Abstract]:Objective to study the effect and mechanism of hepatobiliary juice acid synthesis and transport abnormality in the occurrence of colitis cholestasis. Methods Wistar male rats were randomly divided into 2 groups according to body weight: normal group and model group. Model group rats were given 2,4,6- three nitrobenzene sulfonic acid colon perfusion to prepare ulcerative colitis (UC) model, and normal group rats colon was given. 0.9%Na Cl. was used to examine the activity index of the animals, the score of pathological tissue and the activity of myeloperoxidase; the content of serum alkaline phosphatase (ALP), glutamyl transaminopeptidase (GGT), cereal transaminase (AST) and alanine transaminase (ALT) were measured; the content of total bile acid, deoxycholic acid and stone cholic acid in the liver was measured by liquid chromatography; immunoblotting was used. The expression of the restriction enzyme cholesterol 7 alpha hydroxylase (Cyp7a1) and the multidrug resistance related protein 2 (Mrp2) of the bile acid efflux transporter in the hepatic bile acid synthesis was measured by technique. The results were compared with the normal group, and the pathological changes were 4.51 + 1.49, (1.36 + 0.69) and (0.40 + 0.07) U mg~ (-1) in the model group. The difference was statistically significant (P0.05), indicating that the UC model was successfully prepared. The total bile acid and deoxycholic acid content in the rat model group were (85.50 + 18.60) Mu mol / L~ (-1) and (79.53 + 32.99) ng g~ (-1), and the serum ALP and GGT levels were respectively (259.43 + 58.58), (1.50 + 0.68) U L~ (all), and there were significant differences compared with those of the normal group. P0.05) indicated the existence of intrahepatic cholestasis in the rat model group. Compared with the normal group, the expression of Cyp7a1 in the model group was 0.72 + 0.07, while the expression of the transporter Mrp2 was 0.66 + 0.04, and the difference was statistically significant compared with the normal group (all P0.05). Increased bile acid synthesis and decreased bile acid efflux.
【作者单位】：兰州大学第一医院药剂科;兰州大学药学院;兰州大学第二医院;
【基金】：国家自然科学基金青年科学基金资助项目(81400596) 兰州大学中央高校基本科研专项基金资助项目(lzujbky-2014-223-lzujbky-2015-38)
【分类号】：R574.62

【相似文献】