Javitt N B, Emerman S
J Clin Invest. 1968 May;47(5):1002-14. doi: 10.1172/JCI105790.
Sodium taurolithocholate and sodium taurocholenate were infused intravenously into rats and hamsters. Each bile acid salt was given alone or in combination with varying amounts of a primary bile salt, either sodium taurocholate or sodium taurochenodeoxycholate. Bile flow, total bile acid salt excretion, and the excretion of sodium taurolithocholate were quantitatively determined. In addition, mannitol excretion in bile was determined at various flow rates. Sodium taurolithocholate was found to be rapidly excreted in bile in concentrations greater than its aqueous solubility. When the endogenous excretion rate of bile salt or the infusion of primary bile salt was less than the molar amount of administered sodium taurolithocholate, cholestasis always occurred. Increasing molar amounts of primary bile salt prevented cholestasis and enhanced the excretion rate of sodium taurolithocholate. Infusion of sodium taurocholenate, a nonhemolytic bile salt, caused an effect on bile flow and bile acid salt excretion qualitatively similar to sodium taurolithocholate. The induction of cholestasis can be attributed to the physical properties of these poorly water soluble bile salts. The reduction in bile flow could not be shown to be related to water reabsorption from the biliary tree since there was no increase in mannitol concentration in bile during cholestasis. Reduction in bile flow may be related to obstruction of segments of the biliary tree by precipitates of sodium taurolithocholate and possibly to a decrease in water entry into the biliary tree during infusion of this bile acid salt.
将牛磺石胆酸钠和牛磺胆酸钠静脉注射到大鼠和仓鼠体内。每种胆酸盐单独给药,或与不同量的初级胆盐(牛磺胆酸钠或牛磺鹅去氧胆酸钠)联合给药。定量测定胆汁流量、总胆酸盐排泄量以及牛磺石胆酸钠的排泄量。此外,还测定了不同流速下胆汁中甘露醇的排泄量。发现牛磺石胆酸钠在胆汁中的排泄速度很快,其浓度高于其水溶性。当胆盐的内源性排泄率或初级胆盐的输注量低于所给予的牛磺石胆酸钠的摩尔量时,总是会发生胆汁淤积。增加初级胆盐的摩尔量可防止胆汁淤积,并提高牛磺石胆酸钠的排泄率。输注非溶血胆盐牛磺胆酸钠对胆汁流量和胆酸盐排泄的影响在性质上与牛磺石胆酸钠相似。胆汁淤积的诱导可归因于这些水溶性差的胆盐的物理性质。胆汁流量的减少与从胆管树重吸收水分无关,因为在胆汁淤积期间胆汁中甘露醇浓度没有增加。胆汁流量的减少可能与牛磺石胆酸钠沉淀物阻塞胆管树的部分有关,也可能与在输注这种胆酸盐期间进入胆管树的水分减少有关。