Department of Women and Children's Health, King's College London, Guy's Campus, Hodgkin Building, SE1 1UL London, United Kingdom.
National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, Du Cane Road, W12 0NN London, United Kingdom.
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1345-1355. doi: 10.1016/j.bbadis.2017.12.039. Epub 2018 Jan 6.
Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids.
心脏功能障碍在原发性胆汁性胆管炎和原发性硬化性胆管炎等合并肝硬化的疾病中更为常见。这一观察结果促使人们研究胆汁酸代谢异常与心脏病理之间的关系。大约 50%的肝硬化病例会发展为肝硬化性心肌病。胆汁酸直接参与其中,导致 QT 间期延长、心肌肥厚、心肌细胞凋亡和心脏血液动力学异常。妊娠肝内胆汁淤积症中母体血清胆汁酸升高,这种疾病导致胎-母胆汁酸梯度受损,与致命的胎儿心律失常有关。血清胆汁酸池中单一胆汁酸的疏水性具有相关性,相对亲脂性胆汁酸对心脏的有害影响更大。熊去氧胆酸可以逆转或预防这些升高的胆汁酸对心脏的有害作用。