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

P-糖蛋白在胆汁分泌机制中的分子和病​​理学研究

• 批准号: 07670616
• 负责人: WATANABE Norihito
• 金额: $ 1.47万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670616/
• 关键词: P-glycoprotein; mdr; Bile Secretion; Cholestasis; Bile Canaliculi; cMOAT; MDR

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.

通过免疫组织化学检查了 P-糖蛋白在胆汁淤积条件下的定位，以阐明其在胆汁分泌机制中的功能意义。在对照大鼠胆小管上观察到P-糖蛋白(mdr1,2)的反应产物。在细胞松弛素B和石胆酸诱导的肝内胆汁淤积中，反应产物减少，胆小管收缩显着受损，胆小管扩张。另一方面，P-糖蛋白的活性在胆总管结扎后第1.3天增加，并在第7天减少。通过RT-PCR产物的Southern印迹评估阻塞性黄疸中mdr1b、mdr2和cMOAT基因的表达。在对照大鼠中检测mdr1b、mdr2和cMOAT的表达。胆管阻塞在结扎后第1、3、7天诱导mdr1b、mdr2 mRNA表达，而cMOAT mRNA表达不受影响。这些发现表明 mdr2 和 mdr1 可能与胆汁分泌机制有关。

项目成果

Watanabe N et al: "The motility of cultured hepatocytes by AVEC-DIC microscopy." Kansaibou Kokkaku. 6. 27-33 (1996)

Watanabe N 等人：“通过 AVEC-DIC 显微镜观察培养的肝细胞的运动性。”

渡辺勲史: "AVEC-DIC microscopyによる培養肝細胞の運動性" 肝細胞骨格研究会誌. 6. 27-33 (1996)

Isao Watanabe：“使用 AVEC-DIC 显微镜观察培养的肝细胞的运动性”肝细胞骨架研究学会杂志 6. 27-33 (1996)。