Dowling R H, Mack E, Small D M
J Clin Invest. 1971 Sep;50(9):1917-26. doi: 10.1172/JCI106684.
Bile salts and phospholipids are both required to solubilize biliary cholesterol. Since interruption of the enterohepatic circulation (EHC) depletes bile of bile salts, we have examined in the rhesus monkey the effects of controlled interruption of the EHC on biliary secretion of bile salt, phospholipid, and cholesterol and on the relative proportions of these components in bile. Immediately after complete interruption of the EHC, bile secretion and bile composition remained normal for 2-3 hr. During the next 3 hr, however, secretion of all components decreased. Bile salt decreased to a greater extent than phospholipid and cholesterol, and the bile was now supersaturated with cholesterol. 12-24 hr after interruption of the EHC, a new steady state was reached in which there was a relative deficiency of bile salt and a relative increase in phospholipid and cholesterol. The resulting bile, although somewhat more saturated with cholesterol, was not supersaturated with cholesterol but was stable with respect to cholesterol solubility. Thus, bile instability conducive to gallstone formation occurs transiently within hours after interruption of the EHC. Prolonged large interruptions in the steady state animal also produce a relative bile salt deficiency, but in this situation cholesterol remains soluble in the bile of these animals because there occurs a concomitant relative increase in phospholipid. When the EHC was only partially interrupted, secretion rates and the relative concentration of bile salt, phospholipid, and cholesterol did not change significantly from control values until more than 20% of the bile was diverted. Modest changes in the relative composition of bile occurred when 33 and 66% of the bile was diverted, and these changes were very similar to those produced by resection of the distal small bowel.
胆汁盐和磷脂都是使胆汁中的胆固醇溶解所必需的。由于肠肝循环(EHC)的中断会耗尽胆汁中的胆汁盐,我们在恒河猴身上研究了EHC的可控中断对胆汁盐、磷脂和胆固醇的胆汁分泌以及胆汁中这些成分相对比例的影响。在EHC完全中断后,胆汁分泌和胆汁成分在2 - 3小时内保持正常。然而,在接下来的3小时内,所有成分的分泌都减少了。胆汁盐的减少程度大于磷脂和胆固醇,此时胆汁中胆固醇过饱和。在EHC中断12 - 24小时后,达到了一个新的稳态,即胆汁盐相对缺乏,而磷脂和胆固醇相对增加。由此产生的胆汁,虽然胆固醇饱和度略高,但并未过饱和,在胆固醇溶解性方面是稳定的。因此,有利于胆结石形成的胆汁不稳定性在EHC中断后的数小时内短暂出现。在稳态动物中长时间的大量中断也会导致胆汁盐相对缺乏,但在这种情况下,胆固醇在这些动物的胆汁中仍可溶解,因为同时磷脂会相对增加。当EHC仅部分中断时,在超过20%的胆汁被分流之前,分泌速率以及胆汁盐、磷脂和胆固醇的相对浓度与对照值相比没有显著变化。当33%和66%的胆汁被分流时,胆汁的相对组成发生了适度变化,这些变化与远端小肠切除所产生的变化非常相似。