Induction of multidrug resistance-associated protein 2 in liver, intestine and kidney of streptozotocin-induced diabetic rats
Induction of multidrug resistance-associated protein 2 in liver, intestine and kidney of streptozotocin-induced diabetic rats
复制标题
链脲佐菌素诱导的糖尿病大鼠肝、肠、肾中多药耐药相关蛋白2的诱导
DOI：
10.3109/00498254.2011.654363
复制
发表时间：
2012-08-01
期刊：
影响因子：
1.8
通讯作者：
Liu, Xiaodong
中科院分区：
文献类型：
--
作者：
Mei, Dan;Li, Jia;Liu, Xiaodong
许多研究表明，Mrp 2在某些生理病理学情况下受到高度调节。本研究旨在探讨糖尿病对大鼠肝、肾、肠多药耐药相关蛋白2（Mrp 2）表达及功能的影响。通过腹腔注射链脲佐菌素（65 mg/kg）诱导糖尿病大鼠，并随机分为糖尿病（DM）大鼠和胰岛素治疗的糖尿病大鼠。用Mrp 2的底物磺溴酞（BSP）评价Mrp 2在体内的功能。排泄实验结果表明，与正常大鼠相比，糖尿病大鼠经胆汁、尿液和肠灌流液排泄BSP的能力明显增强，导致静脉注射45 μmol/kg BSP后血浆清除率升高。Western blot结果显示，糖尿病大鼠肝，肾和肠Mrp 2蛋白水平较高，虽然没有观察到肾脏Mrp 2的差异。胰岛素治疗部分逆转了这些变化。糖尿病诱导的Mrp 2与胆汁流量、胆汁和血浆总胆汁酸（TBA）水平以及血浆结合胆红素的增加平行。糖尿病可增强肝、肾、肠Mrp 2的功能和表达，这可能是由于胰岛素缺乏、TBA和结合胆红素增加所致。
Many studies have demonstrated that Mrp2 is highly regulated in some physiopathological situations. The aim of this study was to investigate effects of diabetes mellitus on function and expression of multidrug resistance-associated protein 2 (Mrp2) in rat liver, kidney and intestine. Diabetic rats were induced by an intraperitoneal administration of streptozotocin (65 mg/kg) and randomly divided into diabetic (DM) rats and insulin-treated diabetic rats. Sulfobromophthalein (BSP), a substrate of Mrp2, was used to evaluate Mrp2 function in vivo. Data from excretion experiments demonstrated that compared with normal rats, diabetes markedly enhanced BSP excretion via bile, urine and intestinal perfusate, which contributed to the elevated plasma clearance of BSP after intravenous administration of 45 μmol/kg BSP. Western blot results showed higher levels of hepatic, renal and intestinal Mrp2 protein in DM rats, although no difference was observed in renal Mrp2. Insulin treatment partly reversed these alterations. Induction of Mrp2 by diabetes was in parallel with the increase in bile flow, levels of biliary and plasma total bile acid (TBA), and plasma conjugated bilirubin in DM rats. Diabetes may enhance Mrp2 function and expression in liver, kidney and intestine, which might be due to insulin deficiency, increased TBA and conjugated bilirubin.