Alvaro D, Benedetti A, Gigliozzi A, Bini A, Della Guardia P, La Rosa T, Jezequel A M, Capocaccia L
II Department of Gastroenterology, University of Rome La Sapienza, Italy.
Hepatology. 1995 Apr;21(4):1120-9.
We investigated whether bile salts (BS) with different hydrophobic-hydrophilic properties interact with ethanol on bile secretion, enzyme (aspartate transaminase [AST], lactate dehydrogenase [LDH]) release in the perfusate, liver ultrastructure, and vesicular exocytosis in the isolated perfused rat liver. Ethanol (0.1 or 1%) promoted a rapid decrease of bile flow and BS secretion in livers perfused with taurocholate (TCA), the physiologic BS in the rat (-28% decrease of baseline values with 0.1% and -34% with 1% ethanol). The inhibitory effect of ethanol on bile flow and BS secretion was significantly (P < .02) attenuated by perfusing liver with the hydrophilic BS, tauroursodeoxycholate (TUDCA), and it was exacerbated (P < .02) by perfusion with the hydrophobic BS, taurodeoxycholate (TDCA). The release of AST and LDH in the perfusate was unaffected by 0.1% ethanol, but increased threefold to fivefold by 1% ethanol in TCA-perfused livers. This cytolitic effect of ethanol was not observed in TUDCA-perfused livers, but it was enhanced (P < .03) by perfusion with TDCA. No ultrastructural abnormalities were found in either TCA- or TUDCA-perfused livers, with or without 1% ethanol. Only minimal changes were found in livers perfused with TDCA alone, but, in the presence of TDCA, 1% ethanol induces marked mitochondrial damage. The biliary excretion of the fluid phase marker horseradish peroxidase was inhibited by ethanol, an effect reversed by TUDCA (P < .02) and exacerbated by TDCA (P < .04). In conclusion, this study demonstrates that hydrophilic BS such as TUDCA counteract the inhibitory effect of ethanol on bile secretion and vesicular exocytosis as well as the ethanol-induced cytolitic effect in the isolated perfused rat liver. In the presence of hydrophobic BS such as TDCA, the exposure to ethanol promotes a marked inhibition of bile secretion and vesicular exocytosis as well as prominent mitochondrial damage.
我们研究了具有不同疏水 - 亲水性的胆盐（BS）是否与乙醇在胆汁分泌、灌流液中酶（天冬氨酸转氨酶[AST]、乳酸脱氢酶[LDH]）释放、肝脏超微结构以及离体灌流大鼠肝脏的囊泡胞吐作用方面存在相互作用。乙醇（0.1%或1%）促使灌注牛磺胆酸盐（TCA，大鼠体内的生理性胆盐）的肝脏胆汁流量和胆盐分泌迅速减少（0.1%乙醇使基线值降低28%，1%乙醇使基线值降低34%）。用亲水性胆盐牛磺熊去氧胆酸（TUDCA）灌注肝脏可显著（P <.02）减弱乙醇对胆汁流量和胆盐分泌的抑制作用，而用疏水性胆盐牛磺脱氧胆酸（TDCA）灌注则会加剧（P <.02）这种抑制作用。灌流液中AST和LDH的释放不受0.1%乙醇的影响，但在TCA灌注的肝脏中，1%乙醇使其增加了三到五倍。在TUDCA灌注的肝脏中未观察到乙醇的这种细胞溶解作用，但用TDCA灌注会增强（P <.03）这种作用。在灌注TCA或TUDCA的肝脏中，无论有无1%乙醇，均未发现超微结构异常。单独用TDCA灌注的肝脏仅发现极小的变化，但在存在TDCA的情况下，1%乙醇会导致明显的线粒体损伤。乙醇抑制了液相标记物辣根过氧化物酶的胆汁排泄，TUDCA可逆转这一作用（P <.02），而TDCA会加剧（P <.04）这一作用。总之，本研究表明，亲水性胆盐如TUDCA可抵消乙醇对胆汁分泌和囊泡胞吐作用的抑制作用以及乙醇诱导的离体灌流大鼠肝脏细胞溶解作用。在存在疏水性胆盐如TDCA的情况下，接触乙醇会显著抑制胆汁分泌和囊泡胞吐作用，并导致明显的线粒体损伤。
