Nakai K, Tazuma S, Ochi H, Chayama K
First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
Biochim Biophys Acta. 2001 Dec 30;1534(2-3):78-84. doi: 10.1016/s1388-1981(01)00173-1.
Bilirubin is found in the center of cholesterol gallstones, but its pathogenic role in their formation is unknown. Bilirubin causes a disproportionate reduction of biliary lipid secretion without affecting bile salt secretion in association with a change of biliary lecithin species, which modulates the cholesterol crystallization process. Therefore, the present study investigated whether bilirubin can influence the cholesterol crystallization procedure, and the mechanism(s) of any such action. Supersaturated model bile was prepared (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 9.0 g/dl, and cholesterol saturation index of 1.8), and cholesterol crystallization was monitored over time using a spectrophotometer and video-enhanced differential contrast microscopy in the absence or presence of bilirubin (at a final concentration of 10 microM, 20 microM, 40 microM, and 100 microM). Bilirubin enhanced the onset of cholesterol crystallization by 50%, whereas the crystal growth rate and final crystal mass were reduced at a high concentration of bilirubin. Taken together, these results suggest that bilirubin influences the cholesterol crystallization process, by either a direct interaction with biliary lipids that alters metastability, an indirect alteration of the bile salt-micellar lipid holding capacity, or both. Thus, bilirubin may play a role in the pathogenesis of both cholesterol and pigment gallstones.
胆红素存在于胆固醇胆结石的核心部位，但其在结石形成过程中的致病作用尚不清楚。胆红素可导致胆汁脂质分泌不成比例地减少，而不影响胆汁盐分泌，同时伴有胆汁卵磷脂种类的改变，这会调节胆固醇的结晶过程。因此，本研究调查了胆红素是否会影响胆固醇结晶过程以及任何此类作用的机制。制备了过饱和模型胆汁（牛磺胆酸盐/卵磷脂/胆固醇比例为71:18:11，总脂质浓度为9.0 g/dl，胆固醇饱和指数为1.8），并在不存在或存在胆红素（终浓度为10 microM、20 microM、40 microM和100 microM）的情况下，使用分光光度计和视频增强微分干涉差显微镜随时间监测胆固醇结晶情况。胆红素使胆固醇结晶的起始时间提前了50%，而在高浓度胆红素作用下，晶体生长速率和最终晶体质量降低。综上所述，这些结果表明，胆红素通过与胆汁脂质的直接相互作用改变亚稳定性，或间接改变胆盐 - 胶束脂质容纳能力，或两者兼而有之，从而影响胆固醇结晶过程。因此，胆红素可能在胆固醇结石和色素结石的发病机制中发挥作用。
