Protective role of PTEN inhibition against liver ischemia-reperfusion injury in mice and its underlying mechanisms / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether inhibition of phosphatase and tensin homologue deleted on chromosome ten (PTEN) is protective against liver ischemia-reperfusion injury (IRI) in mice and to explore its possible mechanism.</p><p><b>METHODS</b>Liver IRI was established in C57BL6/J mice by inducing 90 minutes of ischemia in the left/middle liver lobe followed by 6 hours of reperfusion. To investigate the role of PTEN in hepatic IRI, a subset of these mice received pre-treatment with the specific PTEN inhibitor bpv(HOpic), which was injected intraperitoneally at 2 hours prior to the ischemia insult. Serum alanine aminotransferase (sALT) levels were measured and liver histology was assessed in all mice. The levels of pro-inflammatory cytokines IL-12p40 and TNFa were detected by real-time PCR. The expression of p-AKT and p-ERK in liver tissues was analyzed by Western blotting.</p><p><b>RESULTS</b>The IRI group pre-treated with bpv(HOpic) showed significantly lower sALT values (3 075.0 +/- 807.4 U/L vs. IRI without pre-treatment 11 460.0 +/- 1 783.0 U/L, P less than 0.01) and more well-preserved liver architecture. The expression of pro-inflammatory cytokines was inhibited markedly by the administration of bpv(HOpic); for IRI without pre-treatment vs.IRI pre-treated with bpv(HOpic), the IL-12 levels were 1.12 +/- 0.11 vs .0.55 +/- 0.13 ( P less than 0.01) and the TNFa levels were 1.62 +/- 0.20 vs. 0.35 +/- 0.07 ( P less than 0.01). Western blot analysis showed that the hepatic expression of both p-AKT and p-ERK was enhanced obviously in mice pretreated with the PTEN inhibitor.</p><p><b>CONCLUSION</b>PTEN inhibition alleviates hepatic ischemia-reperfusion injury via the up-regulation of pro-survival signaling mediated by p-AKT and p-ERK as well as the inhibition of hepatic inflammation. PTEN may represent a useful target for the treatment of liver IRI.</p>