The role of toll like receptor-4 signal pathways activation in ischemia-reperfusion injury of island skin flap / 中华整形外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To determine the role of toll like receptor-4 signal pathways activation in ischemia-reperfusion injury of island skin flap.</p><p><b>METHODS</b>A totol of 50 adult male SD rats were randomized into 3 groups sham-operated group (n=10), ischemia/reperfusion group (n=20) and TLR4 inhibitor-eritoran tetrasodium (E5564)-treated group (n=20). The inguinal island skin flaps models were set up. A bolus of E5564 (5 mg/kg) was infused intravenously 60 min before reper fusionm. TLR4 binding activity in flap tissue was analyzed at 1, 2, 4 and 6 h of reperfusion by immunohistochemical technique and flaps were assessed histologically at 6 h of reperfusion. The viability of flaps was assessed 7 days postoperatively.</p><p><b>RESULTS</b>Exprerssion TLR4 in skin flap tissue was significantly increased in I/R group, compared with E5564-treated group. Immunohistochemical exam showed TLR4 mainly expressed in skin flap vessel wall and PMN membrane. Marked neutrophil infiltration and edema was observed in I/R group, while less neutrophil infiltration was observed in E5564-treated group. In the E5564-treated group, the survival of flaps was (80.31 +/- 11.63)%, which was significantly greater than that in the I/R group (51.70 +/- 7.62)% (P < 0.01).</p><p><b>CONCLUSION</b>After ischemia-reperfusion injury in rats, the expression of TLR4 increased in the skin flap tissue with excessive neutrophil infiltration. Administration of E5564 can significantly improve flap survival by regulating the early activation of TLR4 and suppressing neutrophil infiltration within the flap.</p>