mdr2突变效应与微管的结合串联破坏糖蛋白转运蛋白环孢霉素对小鼠胆汁的形成。

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Elamiri,帕瓦茨,Tuchweber B,尤瑟夫IM

mdr2突变效应与微管的结合串联破坏糖蛋白转运蛋白环孢霉素对小鼠胆汁的形成。

药物杂志》2003年11月,48 (5):467 - 72。doi: 10.1016 / s1043 - 6618 (03) 00187 - 7。

PubMed ID

12967592 (在PubMed

]

文摘

未标记的:抑制微管的糖蛋白转运蛋白已被认为是家族性肝内胆汁淤积的原因。诱导多药耐药性突变3-glycoprotein (MDR3)基因3型进行性家族性肝内胆汁淤积(PFIC3)。小鼠的表型,突变mdr2像MDR3在人类的破坏。其次,突变的胆汁盐泵出口(BSEP) /妹妹22 (spgp)基因的原因2型在人类进步的家族性肝内胆汁郁积。然而,在spgp淘汰赛老鼠只有温和持久的胆汁淤积发生。本研究的目的是评估各种22 (Pgp)转运蛋白的影响胆汁的形成和微管的运输牛磺胆酸(柠檬酸),试图理解这些转运蛋白的结合作用在家族性肝内胆汁郁积的发病机制。总胆汁酸(稍后通知)和胆酸分泌率下降在mdr2淘汰赛老鼠。然而,胆汁流(BF)和muricholic酸的分泌增加。分泌的胆汁中胆固醇是微不足道的,未发现磷脂的mdr2淘汰赛老鼠。治疗与环孢霉素(CsA)降低了男朋友,和胆汁分泌的胆汁盐(BS)和磷脂与野生型小鼠相比,但在注射柠檬酸+ CsA,男朋友,BS的胆汁分泌和脂质增加比野生型小鼠治疗CsA孤单。 In the mdr2 knock-out mice, CsA treatment decreased the BF and the secretion of BS but after the injection of TCA+CsA, the BF and the biliary secretion of BS were increased and the phospholipid secretion was slightly stimulated as compared to the mdr2 knock-out mice treated with CsA alone. CONCLUSION: Disruption of the mdr2 gene and the inhibition of glycoprotein transporters by CsA induce cholestasis in mice which is characterized by reduced BF, BS and biliary lipid secretion. However, CsA treatment did not significantly increase the cholestatic effect in the mdr2 knock-out mice. The injection of TCA decreased the cholestatic effect in the mdr2 knock-out mice as well as the inhibition of glycoproteins transporters by CsA. These data suggest that mutation in the canalicular mdr2 is an important factor during the development of progressive familial cholestasis.

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药物转运蛋白

药物	转运体	类	生物	药理作用	行动
环孢霉素	微管的multispecific有机阴离子转运体1	蛋白质	人类	未知的	抑制剂	细节