Molecular and Pathological Studies on P-glycoproteins in the Mechanisms of Bile Secretion

p -糖蛋白在胆汁淤积状态下的定位已被免疫组织化学检测，以阐明其在胆汁分泌机制中的功能意义。观察p -糖蛋白（mdr1、2）在对照大鼠胆管上的反应产物。在细胞松弛素B和胆酸诱导的肝内胆汁淤积症中，反应产物减少，胆小管收缩明显受损，胆小管扩张。另一方面，p -糖蛋白活性在胆总管结扎后第1、3天升高，第7天降低。采用RT-PCR产物的Southern印迹法检测mdr1b、mdr2和cMOAT基因在梗阻性黄疸中的表达。在对照大鼠中检测mdr1b、mdr2和cMOAT的表达。胆管梗阻诱导结扎后第1、3、7天mdr1b、mdr2 mRNA表达，而cMOAT mRNA表达不受影响。这些发现提示mdr2和mdr1可能与胆汁分泌机制有关。

The localization of P-glycoproteins in cholestatic conditions has been examined by immunohistochemistry to elucidate its functional significance in the mechanisms of bile secretion. The reaction products ofP-glycoproteins (mdr1,2) were observed on bile canaliculi in control rats. In intrahepatic cholestasis induced by cytochalasin B and lithocholic acid, the reaction products were decreased, and bile canalicular contractions were remarkably impaired with dilatation of the canaliculi. On the other hand, the activities of P-glycoproteins were increased on 1,3 day after common bile duct ligation, and dimished on day 7. The expression of mdr1b, mdr2 and cMOAT genes in obstructive jaundice was assessed by Southern blotting for RT-PCR products. The expression of mdr1b, mdr2 and cMOAT was detected in control rats. The bile duct obstruction induced mdr1b, mdr2 mRNA expressions on day 1,3,7 after ligation, while the expression of cMOAT mRNA was not affected. These findings suggest that mdr2 as well as mdr1 may be associated with the mechanisms of bile secretion.