On the Mechanisms of Biliary Flux
On the Mechanisms of Biliary Flux
复制标题
胆汁通量的机制
DOI：
10.1002/hep.32027
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发表时间：
2021
期刊：
影响因子：
13.5
通讯作者：
Hengstler Jan G.
中科院分区：
文献类型：
--
作者：
Vartak Nachiket;Drasdo Dirk;Geisler Fabian;Itoh Tohru;P.J.Oude Elferink Ronald;van de Graaf Stan F.J.;Chiang John;Keitel Verena;Trauner Michael;Jansen Peter;Hengstler Jan G.
自20世纪50年代末以来，胆汁在肝脏中的运输一直被描述为“渗透概念”，根据该概念，胆汁流入小管，流向管道，与血液在窦状动脉中的流动相反。然而，由于小管的体积小，到目前为止还无法观察到，更不用说量化这个过程了。尽管如此，“渗透性小管流动”对于胆汁中排泄的各种胆汁性化合物的清除特性是一个充分和合理的解释。成像技术现在已经建立，允许直接通量分析在活的生物体的完整肝脏的胆管。与流行的渗透概念相反，这些分析强烈表明，小分子在小管胆汁中的运输以扩散为主，而小管流动可以忽略不计。相反，用同样的实验方法，可以证明在小叶间管中，血流增强了扩散。因此，胆管可以比作与河流相连的死水区。弥散和流动之间看似微妙的差异与包括胆汁淤积和NAFLD在内的广泛肝脏疾病的治疗相关。在这里，我们结合了有关管状溶质运输的最新发现，并将其与现有知识结合起来，提出了一个完整的、可解释的胆汁通量框架，该框架无疑将在未来进一步完善。
Since the late 1950s, transport of bile in the liver has been described by the “osmotic concept,” according to which bile flows into the canaliculi toward the ducts, countercurrent to the blood flow in the sinusoids. However, because of the small size of canaliculi, it was so far impossible to observe, let alone to quantify this process. Still, “osmotic canalicular flow” was a sufficient and plausible explanation for the clearance characteristics of a wide variety of choleretic compounds excreted in bile. Imaging techniques have now been established that allow direct flux analysis in bile canaliculi of the intact liver in living organisms. In contrast to the prevailing osmotic concept these analyses strongly suggest that the transport of small molecules in canalicular bile is diffusion dominated, while canalicular flow is negligibly small. In contrast, with the same experimental approach, it could be shown that in the interlobular ducts, diffusion is augmented by flow. Thus, bile canaliculi can be compared to a standing water zone that is connected to a river. The seemingly subtle difference between diffusion and flow is of relevance for therapy of a wide range of liver diseases including cholestasis and NAFLD. Here, we incorporated the latest findings on canalicular solute transport, and align them with extant knowledge to present an integrated and explanatory framework of bile flux that will undoubtedly be refined further in the future.
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影响因子：
3.7
作者：
Bodewes FA;Bijvelds MJ;de Vries W;Baller JF;Gouw AS;de Jonge HR;Verkade HJ
通讯作者：
Verkade HJ
影响因子：
15.9
作者：
BOYER, JL;BLOOMER, JR
通讯作者：
BLOOMER, JR
影响因子：
15.9
作者：
Joers, Simone;Jeliazkova, Petia;Geisler, Fabian
通讯作者：
Geisler, Fabian
影响因子：
--
作者：
Li, Tingting;Holmstrom, Sam R.;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.
影响因子：
5.2
作者：
R. Rosenthal;D. Günzel;Dian Theune;Carolina Czichos;J. Schulzke;M. Fromm
通讯作者：
R. Rosenthal;D. Günzel;Dian Theune;Carolina Czichos;J. Schulzke;M. Fromm