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胆汁酸吸收不良与结肠炎急性期的腹泻有关。

Bile acid malabsorption is associated with diarrhea in acute phase of colitis.

作者信息

Hou Rui-Gang, Fan Lei, Liu Jun-Jin, Cheng Yao, Chang Zhuang-Peng, Wu Bei, Shao Yun-Yun

机构信息

a School of Pharmaceutical, Shanxi Medical University, Shanxi 030000 China.

b Department of Pharmacy, Second Hospital of Shanxi Medical University, Shanxi 030000, China.

出版信息

Can J Physiol Pharmacol. 2018 Dec;96(12):1328-1336. doi: 10.1139/cjpp-2018-0017. Epub 2018 Nov 1.

Abstract

The enterohepatic circulation of bile acids (BAs) critically depends on BA transporters and enzymes, which can be affected by inflammatory bowel disease. Diarrhea in colitis is believed to result in part from BA malabsorption. The work aimed to investigate whether diarrhea in colitis was associated with the expression of BA transporters, enzymes, and nuclear receptors. RT-qPCR and Western blot techniques were used to evaluate the gene and protein levels of Cyp7a1, Asbt, SHP, FXR, Ostβ in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of colitis. The total BAs (TBAs) levels were assayed using ELISA kits, and the individual BAs were measured by LC-MS/MS. Results showed that the fecal excretions of TBAs were significantly increased by 1.6-fold in acute stage of colitis. In ileum, Asbt was significantly decreased; however, there was a compensatory increase in Cyp7a1 level in liver. Moreover, FXR has a decreased tendency and the downstream target gene SHP was downregulated. Contrary to acute stage, molecular changes were completely reversible during the remission phase. Our results indicated that the expression of Asbt and Cyp7a1 were altered in acute colitis, which performed vital roles in maintaining BA homeostasis. Early medical manipulation of BA transporters and enzymes may help prevent diarrhea.

摘要

胆汁酸(BAs)的肠肝循环严重依赖于BA转运蛋白和酶,而这些可能会受到炎症性肠病的影响。结肠炎中的腹泻被认为部分是由BA吸收不良导致的。这项研究旨在调查结肠炎中的腹泻是否与BA转运蛋白、酶和核受体的表达有关。在2,4,6-三硝基苯磺酸诱导的大鼠结肠炎模型中,采用RT-qPCR和蛋白质印迹技术评估Cyp7a1、Asbt、SHP、FXR、Ostβ的基因和蛋白水平。使用ELISA试剂盒检测总胆汁酸(TBAs)水平,通过液相色谱-串联质谱法测定各胆汁酸水平。结果显示,在结肠炎急性期,粪便中TBAs的排泄量显著增加了1.6倍。在回肠中,Asbt显著降低;然而,肝脏中Cyp7a1水平有代偿性升高。此外,FXR有下降趋势,其下游靶基因SHP被下调。与急性期相反,在缓解期分子变化完全可逆。我们的结果表明,Asbt和Cyp7a1的表达在急性结肠炎中发生改变,它们在维持BA稳态中发挥着重要作用。对BA转运蛋白和酶进行早期医学干预可能有助于预防腹泻。

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