目的检测正常大鼠肝脏不同部位胆管细胞胆汁酸转运蛋白表达的差异。方法用酶消化辅助机械分离方法获得SD大鼠胆管组织并分为大、小胆管组织,应用免疫组织化学、Real time PCR及Western blot等方法检测大鼠胆道系统顶侧钠依赖性胆汁酸转...目的检测正常大鼠肝脏不同部位胆管细胞胆汁酸转运蛋白表达的差异。方法用酶消化辅助机械分离方法获得SD大鼠胆管组织并分为大、小胆管组织,应用免疫组织化学、Real time PCR及Western blot等方法检测大鼠胆道系统顶侧钠依赖性胆汁酸转运体(ASBT)、回肠胆汁酸结合蛋白(IBABP)和基底侧有机溶质转运体α(OSTα)表达,分析其定位及分布的差异。结果 ASBT表达于胆管细胞顶侧胞膜,IBABP表达于细胞浆,Ostα表达于胆管细胞基底侧胞膜。ASBT和IBABP主要表达于大胆管上皮细胞,大胆管组织中ASBT和IBABP的表达量显著高于小胆管组织(P<0.05);而Ostα则同时表达于大胆管和小胆管上皮细胞,其表达量在大、小胆管组织中无显著差异(P>0.05)。结论胆管细胞对胆汁酸的重吸收主要发生于大胆管。展开更多
Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pa...Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.展开更多
Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is uncle...Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.展开更多
文摘目的检测正常大鼠肝脏不同部位胆管细胞胆汁酸转运蛋白表达的差异。方法用酶消化辅助机械分离方法获得SD大鼠胆管组织并分为大、小胆管组织,应用免疫组织化学、Real time PCR及Western blot等方法检测大鼠胆道系统顶侧钠依赖性胆汁酸转运体(ASBT)、回肠胆汁酸结合蛋白(IBABP)和基底侧有机溶质转运体α(OSTα)表达,分析其定位及分布的差异。结果 ASBT表达于胆管细胞顶侧胞膜,IBABP表达于细胞浆,Ostα表达于胆管细胞基底侧胞膜。ASBT和IBABP主要表达于大胆管上皮细胞,大胆管组织中ASBT和IBABP的表达量显著高于小胆管组织(P<0.05);而Ostα则同时表达于大胆管和小胆管上皮细胞,其表达量在大、小胆管组织中无显著差异(P>0.05)。结论胆管细胞对胆汁酸的重吸收主要发生于大胆管。
基金Supported by Grants from FONCYT(PICT 2007,No.00966, PICT 2010,No.2127)CONICET(PIP 2009-2011,No.1665, PIP2012-2015,No.00014)UNR PID(2008-2011/2012-2015)
文摘Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.
文摘Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.
