Miquel J F, Moreno M, Amigo L, Molina H, Mardones P, Wistuba I I, Rigotti A
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Marcoleta 367, Santiago, Chile.
Gut. 2003 Jul;52(7):1017-24. doi: 10.1136/gut.52.7.1017.
Biliary lipid absorption by the gall bladder mucosa and the cholesterol content of the gall bladder wall appear to play a role in cholesterol gall stone formation. As the scavenger receptor class B type I (SR- BI) regulates cellular cholesterol uptake, we studied its expression in human and murine gall bladders, its regulation by increased biliary lipid content, and its role in gall stone formation.
Using immunohistochemistry, SR-BI was found in the apical domain of human gall bladder epithelial cells. Immunoblotting of isolated membranes from gall bladder epithelial cells showed a specific signal for the 82 kDa SR-BI protein. In C57BL/6 mice, SR-BI was also found in the gall bladder epithelium. Using western blot analysis, an inverse relationship was observed between biliary cholesterol concentration and SR-BI expression in murine gall bladder mucosa. By comparing lithogenic diet fed wild-type and SR-BI deficient mice, gall bladder wall cholesterol content and gall stone formation were not found to be dependent on SR-BI expression.
(i) SR-BI is expressed in both human and murine gall bladder epithelium; (ii) biliary cholesterol hypersecretion is associated with decreased gall bladder SR-BI expression in mice; and (iii) murine SR-BI is not essential in controlling gall bladder wall cholesterol content and gall stone formation during diet induced cholelithiasis.
胆囊黏膜对胆汁脂质的吸收以及胆囊壁的胆固醇含量似乎在胆固醇胆结石形成过程中发挥作用。由于B类I型清道夫受体(SR-BI)调节细胞对胆固醇的摄取,我们研究了其在人和小鼠胆囊中的表达、胆汁脂质含量增加对其的调节作用以及它在胆结石形成中的作用。
通过免疫组织化学方法,发现SR-BI存在于人类胆囊上皮细胞的顶端区域。对分离的胆囊上皮细胞膜进行免疫印迹分析显示,82 kDa的SR-BI蛋白有特异性信号。在C57BL/6小鼠中,也在胆囊上皮中发现了SR-BI。通过蛋白质印迹分析,观察到小鼠胆囊黏膜中胆汁胆固醇浓度与SR-BI表达呈负相关。通过比较喂食致石性饮食的野生型和SR-BI缺陷小鼠,发现胆囊壁胆固醇含量和胆结石形成并不依赖于SR-BI的表达。
(i)SR-BI在人和小鼠胆囊上皮中均有表达;(ii)胆汁胆固醇分泌过多与小鼠胆囊SR-BI表达降低有关;(iii)在饮食诱导的胆石症过程中,小鼠SR-BI对控制胆囊壁胆固醇含量和胆结石形成并非必需。