Effect Of Remifentanil On TLR4MRNA Expression And Nf-κB Activation In Rat Renal Ischemia Reperfusion Injury

Objective：Renal ischemia-reperfusion (ischemia/reperfusion, I/R) inju-ry is a major pathophysiological base of acute renal failure, and is a majo-r cause of delayed graft function recovery or even loss of function. Ischem-ia-reperfusion injury is characterized by local and systemic inflammatoryresponse. TLR4is type I transmembrane receptor.Its intracellular region thr-ough intermolecular reaction activate downstream signaling pathways, lea-ding to NF-κB translocation into the nucleus, starting gene transcription r-elated to inflammatory mediators, then induce the body to produce casc-ading waterfall inflammatory response involved in renal ischemia-reperfusi-on injury. This study was to evaluate the influence of remifentanil on ren-al ischemia reperfusion injury TLR4mRNA and NF-κB expression.Methods：Sixty male SD rats,were randomly divided into3groups:sham-operated group (S), ischemia reperfusion group(I/R) and remifentanilgroup (R). Clamp bilateral renal artery to prepared kidney I/R injury model inI/R and R group. S group only exposed bilateral renal artery but withoutclipping. The tail vein was percutaneous cannulated for continuous infusionremifentanil1.0μg.kg-1.min-1in R group or equal saline in S group and I/Rgroup15min Abdominal wound was sutured. Maintain animal bodytemperature36-37℃during experimental process.15min before ischemia,reperfusion1,3,6,24h, take the kidney of four rats in each group, lightmicroscope to observe renal histopathology, Western and RT-PCRdeterminating TLR4mRNA and NF-κ B p65protein of cell nucleusexpression. Measurement data were expressed as mean±standard deviation,comparation using one-way ANOVA within-group and between groups,The difference was statistically significant according to P＜0.05.Results： 1Light microscopy observation: S group at each time point, the I/Rand R group15min before ischemia, kidney tissue showed no significantpathological damage; reperfusion1h and3h, I/R group renal tubularepithelial cells can be seen mild degeneration and necrosis, renal tubular lume-n expansion, reperfusion at6h, glomerular pyknosis, tubular lumen expans-ion seen obvious, interstitial edema,hyperemia, reperfusion24h, the injurieswere aggravated, nuclear condensation, inflammatory cells infiltration rea-ched a peak. Reperfusion at1h,3h,6h in R group, renal pathologicalchange is similar, only mild swelling of the renal tubular epithelialcells, a small amount of variability, no significant change in interstitial; At24h ofreperfusion, renal tubular epithelialcell degeneration and necrosis, injuryaggravated compared with3h and6h. R group renal pathological injury al-leviater than I/R group.2Expression of TLR4mRNA: Compared with15min before ische-mia and S group, I/R group TLR4mRNA expression upregulate at1h,3h,6h、24h after reperfusion (P<0.05or0.01); Compared with I/R group,R group TLR4mRNA downregulated (P<0.05or0.01).3Expression of NF-κB p65protein of cell nucleus. NF-κB: Compared with15min before ischemia and S group, I/R group NF-κB expression increased at1h、3h、6h、24h after reperfusion (P<0.05or0.01); Compared with I/R group, R group NF-κB decreased (P<0.05or0.01).Conclusion：Remifentanil can reduce renal ischemia reperfusion inju-ry by inhibition the of TLR4mRNA expression and NF-κB activation.