Kanai S, Ohta M, Kitani K, Sato Y
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.
Life Sci. 1990;47(26):2421-8. doi: 10.1016/0024-3205(90)90486-b.
Cholestasis and enhanced biliary leakage of proteins such as lactate dehydrogenase (LDH) and albumin are known to be induced by infusions of relatively toxic bile salts such as taurocholate (TC) and taurochenodeoxycholate (TCDC). Tauroursodeoxycholate (TUDC) was previously shown to prevent these bile abnormalities when simultaneously infused (1-5). In the present study, we examined whether tauro beta-muricholate (T beta-MC) has a similar effect. The enhanced biliary excretion of LDH and albumin induced by the infusion of TCDC at a rate of 0.4 mumol/min/100 g was markedly prevented by the simultaneous infusion of T beta-MC or TUDC at a rate one-fourth that of TCDC. Increased LDH level in plasma and hemolysis caused by the infusion of TCDC were also reduced by either T beta-MC or TUDC. These results indicate that T beta-MC has a preventive effect on TCDC-induced hepatobiliary changes, which is as efficient as that of TUDC as shown previously, suggesting that the 7 beta-hydroxy group is important for this hepatoprotective effect. Furthermore, our results suggest that beta-muricholic acid may also have clinical value since current reports demonstrate a beneficial effect of ursodeoxycholic acid on a variety of cholestatic conditions, including primary biliary cirrhosis.
已知输注相对有毒的胆盐如牛磺胆酸盐(TC)和牛磺鹅去氧胆酸盐(TCDC)会导致胆汁淤积以及蛋白质如乳酸脱氢酶(LDH)和白蛋白的胆汁渗漏增强。先前研究表明,同时输注牛磺熊去氧胆酸盐(TUDC)可预防这些胆汁异常(1 - 5)。在本研究中,我们检测了牛磺β - 鼠胆酸盐(Tβ - MC)是否具有类似作用。以0.4 μmol/min/100 g的速率输注TCDC所诱导的LDH和白蛋白胆汁排泄增强,通过以TCDC四分之一的速率同时输注Tβ - MC或TUDC可得到显著预防。Tβ - MC或TUDC还可降低输注TCDC所致的血浆LDH水平升高和溶血。这些结果表明,Tβ - MC对TCDC诱导的肝胆变化具有预防作用,其效果与先前所示的TUDC一样有效,这表明7β - 羟基对于这种肝脏保护作用很重要。此外,我们的结果表明β - 鼠胆酸可能也具有临床价值,因为目前的报告显示熊去氧胆酸对包括原发性胆汁性肝硬化在内的多种胆汁淤积性疾病具有有益作用。