Correlation of the protein expression of organic anion transport polypeptide 1 and multidrug resistance-associated protein 2 on the surface of hepatocyte membrane with signal intensity on Gd-EOB-DTPA-enhanced magnetic resonance imaging in dogs with acute liver failure

Objective To investigate the correlation of signal intensity on Gd-EOB-DTPA-enhanced magnetic resonance imaging(MRI) with the expression of organic anion transport polypeptide 1(OATP1) and multidrug resistance-associated protein 2(MRP2) on the surface of hepatocyte membrane.Methods A total of 16 healthy adult male beagle dogs were randomly divided into control group and acute liver failure group,with 8 dogs in each group.Gd-EOB-DTPA-enhanced MRI was performed for the dogs in the acute liver failure group at 24 hours after modeling to measure the signal intensity of different signal areas of liver parenchyma and the percentage of enhancement slope in the first-pass rapid rise period,and according to the MRI images of the hepatocyte phase(20 minutes after the injection of Gd-EOB-DTPA),the high-,medium-,and low-signal areas were selected for liver biopsy.Gd-EOB-DTPA-enhanced MRI was performed for the dogs in the control group after the injection of an equal volume of normal saline using the method,and liver biopsy was performed in the corresponding area.Western blot was used to measure the expression of the Gd-EOB-DTPA uptake protein OATP1 and its excretion protein MRP2 in liver tissue.An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the independent samples t-test was used for comparison of the protein expression of OATP1 and MRP2 in the same signal area between groups.A Pearson correlation analysis was used to investigate the correlation between protein expression levels and signal intensity.Results The Gd-EOB-DTPA-enhanced MRI images of the beagle dogs with acute liver failure showed a significant difference in signal between the high-,medium-,and low-signal areas during hepatocyte phase,and there were also significant differences in the corresponding SIbase value,SIst value,and percentage of enhancement slope during the first-pass rapid rise period(F=70.70,55.12,and 19.82,all P<0.001).In the acute liver failure group,there were significant differences in the expression of OATP1 and MRP2 in liver tissue between different signal areas(F=7.508 and 6.212,both P<0.01),and compared with the control group,the acute liver failure group had a significant reduction in the expression of OATP1 in the medium-and low-signal areas(t=3.301 and 3.641,both P<0.05),which was consistent with the trend of signal reduction in hepatocyte phase;the reduction in the low-signal area was significantly greater than that in the high-signal area(t=3.436,P<0.05) and the medium-signal area(t=2.378,P<0.05).Compared with the control group,the acute liver failure group had a significant increase in the expression of MRP2 in the high-,medium-,and low-signal areas,with a tendency to increase from the high-signal area to the medium-signal area and low-signal area(t=-7.236,-8.130,and-9.614,all P<0.05).Conclusion The expression levels of OATP1 and MRP2 on the surface of hepatocyte membrane are correlated with the degree of enhancement of liver parenchyma in the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI,which provides a certain basis for the segmental assessment of hepatocyte function.