N (Fig. 2b; 30 minutes: two versus 4 mol/L, P 0.031; 6 hours: 3 versus 6 mol/L, P 0.017; 24 hours: two.five versus five mol/L, P 0.012).Intragraft Expression of Egr-1, ET-1, ETA, TNF- , MIP-2, and iNOS: Down-Regulation of Egr-1 PathwayThe intragraft mRNA levels of Egr-1 had been substantially down-regulated at 30 minutes and six hours after LRP-1/CD91 Proteins Recombinant Proteins reperfusion within the FK group (Fig. 3a; 30 minutes: 77 versus 389 DPP IV/CD26 Proteins Source relative to basal level, P 0.034; 6 hours: 15 versus 258 relative to basal level, P 0.034). The intragraft protein levels of Egr-1 were consistent using the mRNA levels (Fig. 4). As for ET-1 and ETA, the intragraft mRNA levels had been decreased significantly at 2 hours, 6 hours, and 24 hours right after liver transplantation (Fig. 3b, 3c; ET-1, 2 hours: 33.five versus 573 relative to basal level, P 0.034; 6 hours: 23 versus 392 relative to basal level, P 0.034; ETA, six hours: 157.five versus 266 relative to basal level, P 0.021;hours: 151 versus 356 relative to basal level, P 0.021). Even though over-expression of intracellular ET-1 was found in both groups at 30 minutes soon after reperfusion (Fig. 5a-1, 5a-3), it decreased drastically at 24 hours immediately after reperfusion inside the FK group (Fig. 5a-2, 5a-4). The intragraft mRNA levels of TNF- have been downregulated within the FK group at 6 hours and 24 hours soon after liver transplantation compared with the manage group (Fig. 3d; 6 hours: 218 versus 682 relative to basal level, P 0.038; 24 hours: 115.five versus 609.six relative to basal level, P 0.02). Each the intragraft mRNA level (Fig. 3e, 24 hours: 113.five versus 672.5 relative to basal level, P 0.04) and protein degree of MIP-2 (Fig. 4) have been down-regulated soon after FK 409 remedy. The intracellular protein expression of iNOS was significantly down-regulated at 24 hours soon after liver transplantation immediately after FK 409 remedy (Fig. 5b-2, 5b-4) compared with the manage group, while the comparable levels on the 2 groups have been discovered at 30 minutes following reperfusion (Fig. 5b-1, 5b-3).Intragraft Expression of HO-1, A20, Hsp-70, Interferon- -Inducible Protein-10 (IP-10), CXCR2, CXCR3, and IL-10: Prior Induction of Hsps and Anti-inflammatory GenesBoth the intragraft mRNA (Fig. 6a, 6b) and protein expressions (Figs. four and 7) of HO-1 and A20 had been up2004 Lippincott Williams WilkinsAnnals of Surgery Volume 240, Quantity 1, JulyFK409 Attenuates Modest Liver Graft InjuryFIGURE 7. Intracellular protein expression of (a) heme oxygenase-1 (HO-1) and (b) A20 in FK group at (1) 30 minutes and (two) 24 hours after reperfusion, and that in manage group at (three) 30 minutes and (four) 24 hours after reperfusion. (HO-1: 400, A20: 200).FIGURE 8. Intracellular protein expression of (a) CXCR2 and (b) interleukin-10 (IL-10) in FK group at (1) 6 hours and (two) 24 hours following reperfusion, and that in control group at (3) 6 hours and (four) 24 hours just after reperfusion. The sinusoidal dilation (arrow) was discovered at 6 hours following reperfusion in handle group (a-3). ( 200).regulated soon after FK 409 treatment during the initially 24 hours following reperfusion. The peak in the mRNA degree of HO-1 in the FK group reached 5393 relative to basal level at six hours after reperfusion compared with the control group (781 relative to basal level, P 0.034) (Fig. 6a). The intragraft protein expression of HO-1 in the FK group was identified at its highest level at 24 hours immediately after reperfusion by Western blot (Fig. four). The intracellular protein expression by immunostaining demonstrated that over-expression of HO-1 was primarily identified in sinusoidal endothelial cel.
