The pathophysiology of cholestasis with special reference to primary biliary cirrhosis

被引:7
|
作者
Jansen, PLM
机构
[1] Univ Groningen Hosp, Dept Gastroenterol & Hepatol, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Gastroenterol, NL-9700 RB Groningen, Netherlands
[3] Univ Groningen Hosp, Res Ctr Gastrointestinal & Metab Dis, NL-9700 RB Groningen, Netherlands
关键词
cholestasis; P-glycoproteins; multidrug-resistance-associated proteins; hepatocytes; cholangiocytes; primary biliary cirrhosis; transport; bile;
D O I
10.1053/bega.2000.0104
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Cholestasis in primary biliary cirrhosis results from impairment of bile flow either by reduced transport at the level of the canaliculi or by disturbed bile flow through damaged intrahepatic bile ductules. Whatever its cause, the expression of hepatic transport proteins will be affected. In cholestatic rats: the expression of the multispecific organic anion transporter mrp2 is decreased; the bile salt export pump bsep and the phospholipid transporter mdr2 are less affected; the carrier protein for hepatic uptake of bile salts ntcp is sharply down-regulated; Mrp3, a basolateral ATP-dependent transporter for glucuronides and bile salts, is upregulated. Thus, bile salts that cannot exit the hepatocyte because of the cholestasis are effectively removed across the basolateral membrane. These may be adaptive responses in defence against overloading of hepatocytes with cytotoxic bile salts. These responses show that the expression of hepatic transporter proteins is highly regulated. This occurs by transcriptional and post-transcriptional mechanisms. Primary biliary cirrhosis starts as a disease of the small intrahepatic bile ducts and therefore the experimental evidence for 'cross-talk' between hepatocytes and cholangiocytes is of great interest for this disease and needs to be further investigated. New insights in bile physiology may enable the development of new therapies for cholestatic liver diseases as primary biliary cirrhosis.
引用
收藏
页码:571 / 583
页数:13
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