Effects Of Different Doses Of Dexmedetomidine On The Expression Of HMGB1-TLR4-MyD88-NF-?B Signaling Pathway In Myocardium Of Rats After Renal Ischemia Reperfusion

Objective:To observe the protective effect of dexmedetomidine preconditioning on myocardium after renal ischemia reperfusion in rats and its mechanism.Methods:40healthy male wistar rats of SpF grade,weighing 250-300g,aged 8-10 weeks,were randomly divided into 5 groups:sham operation group?C group?,renal ischemia reperfusion group?I/R group?,Low dose dexmedetomidine+renal ischemia reperfusion group?L-Dex+I/R group?,Middle dose dexmedetomidine+renal ischemia reperfusion group?M-Dex+I/R group?and High dose dexmedetomidine+renal ischemia reperfusion group?H-Dex+I/R group?.The low,middle and high dose dexmedetomidine groups received intravenous infusion of dexmetomidine 1ug kg^-11 h^-1,2ug kg^-11 h^-11 and 4ug kg^-11 h^-130 min before ischemia until the end of reperfusion.The blood samples were collected from inferior vena cava at 4 h after reperfusion.The concentrations of HMGB1,IL-6,IL-10,IL-17 and TnI were detected by enzyme-linked immunosorbent assay?ELISA?.The expression of HMGB1,TLR4,MyD88,NF-kBp65,p-NF-kBp65 in myocardial tissue was determined by Western blot method,and the expression of HMGB1,TLR4,MyD88 and NF-?Bp65 was detected by RT-pCR method,and the expression and localizationofTLR4andNF-kBp65proteinwereobservedby immunohistochemistry.Results:renalischemia-reperfusioninducedsignificant myocardial injury and increased the concentration of TnI and IL-17 in plasma?p<0.05?.The expression of TLR4 and NF-kBp65 protein and the expression of TLR4,MyD88 and NF-kBp65 mRNA were up-regulated?p<0.05?.The pretreatment with different doses of dexmedetomidine reduced myocardial injury in a dose-dependent manner,and decreased the expression of TLR4 and NF-kBp65 protein and the expression of TLR4,MyD88 and NF-kBp65 mRNA in myocardial tissue?p<0.05?.Conclusion:dexmedetomidine can attenuate myocardial injury after renal ischemia-reperfusion in rats,and the mechanism may be related to the inhibition of HMGB1-TLR4-MyD88-NF-?B signaling pathway.At the same time,the protective effect in the range of clinical used dose has a certain degree of dose dependence.