Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat
Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat
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DOI：
10.1053/gast.2001.29608
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发表时间：
2001-12-01
期刊：
影响因子：
29.4
通讯作者：
Boyer, JL
中科院分区：
文献类型：
--
作者：
Lee, J;Azzaroli, F;Boyer, JL
背景与目的：胆汁淤积导致肝细胞中胆盐转运蛋白的适应性调节，这可能限制肝损伤。然而，目前尚不清楚是否也发生在肝外组织，特别是肾脏，这可能有助于胆盐排泄梗阻性胆汁淤积的胆盐转运蛋白的表达。研究方法：从大鼠胆总管结扎后14天的肝脏和肾脏中分离RNA和蛋白质，并通过RNA保护试验、Western分析和组织免疫荧光进行评估。还在肾脏刷状缘膜囊泡中测定了钠依赖性胆盐转运。结果：胆总管结扎后，血清胆盐先升高，3天后下降至较低水平。相反，尿胆盐排泄量在2周内逐渐上升。到那时，回肠钠依赖性胆盐转运蛋白信使RNA和蛋白质表达在总肝脏中分别增加到对照的300%和200%，而在肾脏中分别为对照的46%和37%。肾刷状缘膜囊泡中H-3-牛磺胆酸钠依赖性摄取减少。相反，肾脏中的多药耐药相关蛋白2表达增加2倍，甚至在结扎后1天。免疫荧光研究证实了这些转运蛋白在肝脏和肾脏中表达的变化。结论：这些研究表明，胆盐转运蛋白在大鼠胆总管梗阻后，在肾脏和胆管细胞的分子表达进行适应性调节。这些反应可能有助于胆汁淤积期间胆盐排泄的肝外途径。
Background & Aims: Cholestasis results in adaptive regulation of bile salt transport proteins in hepatocytes that may limit liver injury. However, it is not known if changes also occur in the expression of bile salt transporters that reside in extrahepatic tissues, particularly the kidney, which might facilitate bile salt excretion during obstructive cholestasis. Methods: RNA and protein were isolated from liver and kidney 14 days after common bile duct ligation in rats and assessed by RNA protection assays, Western analysis, and tissue immunofluorescence. Sodium-dependent bile salt transport was also measured in brush border membrane vesicles from the kidney. Results: After common bile duct ligation, serum bile salts initially rose and then declined to lower levels after 3 days. In contrast, urinary bile salt excretion rose progressively over the 2-week period. By that time, the ileal sodium-dependent bile salt transporter messenger RNA and protein expression in total liver had increased to 300% and 200% of controls, respectively, while failing to 46% and 37% of controls, respectively, in the kidney. Sodium-dependent uptake of H-3-taurocholate in renal brush border membrane vesicles was decreased. In contrast, the multidrug resistance-associated protein 2 expression in the kidney was increased 2-fold, even 1 day after ligation. Immunofluorescent studies confirmed the changes in the expression of these transporters in liver and kidney. Conclusions: These studies show that the molecular expression of bile salt transporters in the kidney and cholangiocytes undergo adaptive regulation after common bile duct obstruction in the rat. These responses may facilitate extrahepatic pathways for bile salt excretion during cholestasis.