Paumgartner Gustav, Pusl Thomas
Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
Clin Liver Dis. 2008 Feb;12(1):53-80, viii. doi: 10.1016/j.cld.2007.11.013.
In most cholestatic liver diseases the cause of the disease is not known and therapy can only be directed toward suppression of the pathogenetic processes and amelioration of the consequences of cholestasis. The recognition of adaptive-compensatory responses to cholestasis has become of major importance. They tend to minimize retention of bile acids and other potentially toxic solutes in the hepatocyte by limiting hepatocellular uptake, reducing bile acid synthesis, stimulating detoxification, and up-regulating alternative pathways for excretion. Some of the drugs used for the treatment of cholestatic liver diseases in an empiric way turned out to be modulators of nuclear receptors, which regulate these adaptive-compensatory responses. New drugs are being designed and tested along these lines and may be regarded as treatment opportunities of the future.
在大多数胆汁淤积性肝病中,病因不明,治疗只能针对抑制致病过程和改善胆汁淤积的后果。认识到对胆汁淤积的适应性代偿反应已变得至关重要。它们倾向于通过限制肝细胞摄取、减少胆汁酸合成、刺激解毒以及上调排泄的替代途径,将胆汁酸和其他潜在有毒溶质在肝细胞中的潴留降至最低。一些以经验方式用于治疗胆汁淤积性肝病的药物被证明是核受体的调节剂,这些核受体调节这些适应性代偿反应。正在沿着这些思路设计和测试新药,它们可能被视为未来的治疗机会。