摘要
胆汁淤积是广泛的胆汁酸合成或胆汁流动的遗传或获得性疾病的主要病原性事件,导致胆汁酸的肝内和全身积累。反过来,增加的胆汁酸水平导致肝细胞损伤和进行性肝损伤,最终导致纤维化和终末期肝病。在受伤的胆汁淤积肝中,细胞凋亡一直被认为是胆汁酸介导的损伤的直接后果。现在显而易见的是炎症和坏死发挥相同甚至更为普遍的作用。熊去氧胆酸是几种胆汁淤积综合征的主要治疗方法,但在某些情况下效力有限。由于miRNA在基本生物过程中起关键作用,而且他们的放松管制在人类肝脏疾病中很常见,miRNA的前瞻性应用作为治疗靶点或疾病生物标志物正在越来越多地得到证实。弄清楚每个参与者的确切贡献对于指导努力寻找急需的胆汁淤积的新型治疗策略至关重要。
关键词: 细胞凋亡、胆汁酸、细胞凋亡、胆汁郁结、微小RNA, 坏死,坏死因子,治疗
图形摘要
Current Drug Targets
Title:Cell Death and microRNAs in Cholestatic Liver Diseases: Update on Potential Therapeutic Applications
Volume: 18 Issue: 8
关键词: 细胞凋亡、胆汁酸、细胞凋亡、胆汁郁结、微小RNA, 坏死,坏死因子,治疗
摘要: Cholestasis is the main pathogenic event in a wide range of genetic or acquired disorders of bile acid synthesis or bile flow, resulting in intrahepatic and systemic accumulation of bile acids. In turn, augmented levels of bile acids lead to hepatocellular injury and progressive liver damage, eventually culminating in fibrosis and end-stage liver disease. In the injured cholestatic liver, apoptosis has long been recognized as a direct consequence of bile acid-mediated injury. It is now apparent that inflammation and necrosis play an equal or even more prevalent role. Ursodeoxycholic acid is the mainstream treatment for several cholestatic syndromes, but has limited efficacy in certain circumstances. With the notion that miRNAs play key roles in basic biological processes and that their deregulation is common in human liver disease, prospective use of miRNAs as either therapeutic targets or disease biomarkers is now being increasingly documented. Deciphering the exact contribution of each player is crucial for directing efforts toward finding much needed novel therapeutic strategies for cholestasis.
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Cell Death and microRNAs in Cholestatic Liver Diseases: Update on Potential Therapeutic Applications, Current Drug Targets 2017; 18 (8) . https://dx.doi.org/10.2174/1389450116666151019102358
DOI https://dx.doi.org/10.2174/1389450116666151019102358 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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