rhGH上调Mrp2表达及促胆红素转运的作用

目的研究 rhGH 上调胆道再通大鼠肝脏 Mrp2表达及促进胆红素排泄的作用机制。方法对胆道梗阻及再通大鼠动物模型的72份血清样本进行放免检测 GH;144份肝组织样本进行间接免疫荧光染色和 RT-PCR,在肝细胞毛细胆管面上染色定位 Mrp2,计算机图像分析测定,半定量比较肝细胞毛细胆管面上 Mrp2表达情况,并与血清生长激素、胆红素作相关分析。结果在胆道梗阻时机体存在 GH 分泌、释放不足从正常时的6.54±1.09下降到14 d 的1.97±0.64,Mrp2转运蛋白特异性定位于肝细胞膜的毛细胆管面,荧光染色呈线条形勾勒出毛细胆管轮廓,给予 rhGH 的胆道再通大鼠肝脏 Mrp2表达水平明显增高,恢复加快。分别由143±8.1、177±12.4和212±15.4升高为159±9.3、209±13.1和221±15.4,并且随着血清 GH、胆红素的升高或降低而发生变化。结论胆道梗阻大鼠行再通术后,Mrp2的蛋白表达水平恢复缓慢,时间长。可能是由于胆道梗阻时 GH 显著下降所致。rhGH 促进胆红素的转运的作用机制可能是通过直接上调 Mrp2表达来实现。

Upregulation of expression of Mrp2 and promotion of bilirubin transport by rhGH

Objective To study the upregulation of expression of Mrp2 and promotion of biliru- bin transport by rhGH in liver tissues of rats with restoration of bile flow(RBF).Methods After common bile duct ligation(CBDL),Wistar rats of 14 days in age were subjected to RBF for test and sham operation.The samples were collected on day 3,7,14 after RBF.Mrp2 of liver tissue was de- termined by irnmunofluorescent microscopy and RT-PCR,serum GH by radioimmunoassay.Mean- while,they correlatively analyzed with GH and bilirubin in the serum.Results After RBF,the ex- pression of Mrp2 increased but the recovery was very slow.The level of Mrp2 in the liver tissue was upregulated by rhGH and was significantly correlated to that of GH in the serum.Conclusions The reason for slow recovery of Mrp2 expression might be down-regulation of serum GH in rats with obstructive jaundice The promotion of bilirubin transport by rhGH can upregulate the expression of Mrp2.