In the IPC+IPO group HIF-1α mRNA expression was significantly lower compared
to the IRI group (IRI vs. IPC+IPO, p ≤ 0.01). The HIF-1α mRNA Salubrinal levels were comparable between group CG, IPC, IPO and IPC+IPO (Figure 3) Figure 3 Expression of HIF-1α mRNA. Expression after 30 min of reperfusion. CG, Control group. IRI, 30 min of ischemia. IPC, IPC + 30 min of ischemia. IPO, 30 min ischemia + IPO. IPC+IPO, IPC + 30 min of ischemia + IPO. * indicates p ≤ 0.01 compared to group IRI. ¤ indicates p = 0.065 compared to group IRI. VEGF expression As shown in Figure 4, VEGF mRNA expression was significantly increased in the IRI group compared to the control group (p ≤ 0.01). When applying IPC+IPO VEGF mRNA expression was also increased compared to the control group (p ≤ 0.038). No significant differences were Veliparib solubility dmso observed between groups IPC, IPO and the control group (IPC vs. CG, p ≤ 0.067) and (IPO vs. CG, p ≤ 0.067). Figure 4 Expression of VEGF mRNA. Expression Ro 61-8048 cell line after 30 min of reperfusion. CG, Control group. IRI, 30 min of ischemia. IPC, IPC + 30 min of ischemia. IPO, 30 min ischemia + IPO. IPC+IPO, IPC + 30 min of ischemia + IPO. *indicates p ≤ 0.01 compared to group CG. **indicates p ≤ 0.038 compared to group CG. TGF-β1 expression No differences in TGF-β1 mRNA expression were observed between the five groups (Figure 5). Figure 5 Expression of TGF-β1 mRNA. Expression after
30 min of reperfusion. CG, Control group. IRI, 30 min of ischemia. IPC, IPC + 30 min of ischemia. IPO, 30 min ischemia + IPO. IPC+IPO, IPC + 30 min of ischemia + IPO. Discussion As expected HIF-1α mRNA expression was increased significantly in rats subjected to 30 minutes of warm liver ischemia and 30 minutes of reperfusion compared to the control group. The main finding of this study was an absent of HIF-1α induction in IPC or IPC+IPO treated animals. In both of these groups, the expression levels were similar to that of CG. In the IPO group the same tendency towards an absent induction of HIF-1α was observed although not significant. VEGF mRNA expression increased significantly when applying 30 min of ischemia without ischemic conditioning compared to sham operated controls. IPC+IPO also showed
increased VEGF mRNA expression compared to sham operated controls, whereas neither ischemia nor ischemic conditioning affected hepatic TGF-β expression. The cytoprotective effects of IPC, Bay 11-7085 defined as brief periods of ischemia and reperfusion prior to prolonged ischemia, on I/R injuries to the liver have become indisputable with an increasing number of studies supporting this fact [12–14]. The IPC protocol used in this study has previously been shown to induce hepatoprotection against I/R injuries. We choose circulating ALAT as marker of hepacellular injuries, as this parameter is well established and known to correlate to the degree of injury [28–30]. However, we were unable to see any hepatoprotective effects as assessed by changes in liver parameters.