| Objectives: To study the potential molecular mechanism in the pathophysiological changes of obstructive jaundice, and provide a possible approach to enhance surgical tolerance and safety, promote recovery. Multidrug resistance-associated protein 1 is a membrane glycoprotein, which pumps its substrates, eg. conjugated bilirubin and bile salts, out of cytosol. Whatever causes cholestasis may derive from, there is a characteristic down-regulation of MRP2, which is considered as the main bilirubin transporter under normal circumstances. At the same time, as a novel inducible bilirubin transporter, the expression of Mrp1 protein, normally expressed at very low levels in hepatocytes, is elevated in endotoxin-induced intrahepatic cholestatic rats, suggesting that Mrp1 mediates the efflux of conjugated bilirubin and divalent bile salt conjugates into plasma followed by urinary elimination, namely a compensatory mechanism under conditions of impaired bile excretion into biliary tree. So far, its expression and clinical significance remain unclear in obstructive jaundice.Methods:1. The expression of MRP1 was detected by indirect immunofluorescence in the liver specimens of twenty control patients without jaundice and thirty patients with obstructive jaundice.2. One hundred and forty six Wistar male rats were randomizedly divided into five groups, namely SHAM, CBDL, CBDL-GH, REF, REF-GH. Experimental model was established by common bile duct ligation(CBDL) and internal drainage 2 weeks later, and rhGH was injected subcutaneously by 0.5u/kg bw per day. Such liver function indices as ALT, ALB, AKP, TBIL in rat serum, in addition to DBIL in rat urine, were assayed by ultraviolet spectrophotometer at each selected timepoint. TNF-αand PA were assayed by RIA and immune turbidity respectively. The expression of Mrp1 was detected by indirect immunofluorescence, which was quantified by average integration optic density.Results:1. The expression of MRP1 in OJ patients' liver specimens was stronger than in control ones.2. One-week mortality of REF-GH group was much lower than REF group (p<0.05).3. Serum ALT, AKP and TNF-α, in addition to urinary DBIL were ascending, while serum ALB and PA descending significantly after CBDL. The level of TBIL peaked on the seventh day postoperatively, followed by a moderate decline. After bile reflow, both serum liver function indices and urinary DBIL were taking a gradually favourable turn and drew near to normal levels. The above-mentioned indices of rhGH-treated rats were much better than that of non-rhGH-treated rats.4. The expression of Mrp1 in SHAM group was so weak that could hardly be detected under fluorescence microscope. However, in CBDL and CBDL-GH groups, obvious fluorescence could be detected from the seventh day postoperatively, showing significant discrepancies when compared with SHAM group. As duration elongated, both the intensity and range of specific fluorescence grew, even after bile reflow, moderate level of fluorescence were maintained with a small amount of descent. Compared with non-rhGH-treated rats at the same timepoints, the expression of Mrp1 in rhGH-treated rats was much stronger, and the discrepencies showed statistical significance when quantified by average integration optic density.5. TNF-αcorrelated positively with ALT and Mrp1, but negatively with PA. When performed significance-checkout, P value was smaller than 0.05, indicating that TNF-αbore close relations to both the deterioration of liver function and the expression of Mrp1 in obstructive jaundiced rats.Conclusions:1. Compared with control group, the expression of MRP1 in OJ group was much stronger, suggesting an important role of MRP1 in obstuctive jaundice.2. The high level of Mrp1 was confirmed in experimental rat model, together with descent of serum TBIL and ascent of urine DBIL in obstructive period, even after bile reflow, moderate expression of Mrp1 was maintained, suggesting a compensatory function of Mrp1 to excrete bilirubin and other bile components...
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