Dexmedetomidine Pretreatment Attenuates Myocardial Ischemia/reperfusion Injury By Activating Cholinergic Anti-inflammatory Pathway

Part One: Dexmedetomidine pretreatment attenuates myocardial ischemia/reperfusion in rats through intact vagal nerveObjective To determine whether dexmedetomidine(Dex)preconditioning could provide cardioprotection against ischemia/reperfusion(I/R)injury through vagal nerve in rats.Methods Sprague Dawley male rats,weighing 230-270 g,were randomly assigned into five groups(n=15,each): sham operation(group S),group I/R,unilateral vagotomy(VG)+I/R(group V),Dex+I/R(group D),VG+Dex+I/R(group VD).In group D and VD,Dex 1ug·kg-1for 10 min followed by 0.7ug·kg-1·h-1 for 15 min was infused via the right jugular vein,and other groups received the same volume of saline.Myocardial I/R model was established with ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min.Infarct size and the area at risk,serum levels of IL-6,TNF-? and cTnI,mRNA expression of IL-6,TNF-? and HMGB1 in myocardium,protein expression of HMGB1 in myocardium were analyzed by Evans Blue and 2,3,5-triphenyltetrazolium chloride,ELISA,real time quantitative PCR,Western blot and immunohistochemistry respectively.Results Compared with group S,infarct size,serum levels of IL-6,TNF-? and cTnI,mRNA expressions of IL-6,TNF-? and HMGB1,and protein expression of HMGB1 in myocardium were significantly increased in I/R group(P<0.05).Compared with group I/R,all measurements above were markedly decreased in group D(P<0.05).Compared with group D,the infarct size was significantly increased and those parameters above were also significantly increased in group VD(P<0.05).Conclusions Dexmedetomidine preconditioning protects the hearts against ischemia/reperfusion injury in rats by alleviating inflammatory response through intact vagal nerve.Part Two: Dexmedetomidine preconditioning attenuates myocardial ischemia/reperfusion in rats through ?7 nicotinic acetylcholine receptorsObjective To determine whether dexmedetomidine preconditioning could provide cardioprotection against ischemia/reperfusion injury through ?7 nicotinic acetylcholine receptors(?7nAchR)in rats.Methods Sprague Dawley male rats,weighing 230-270 g,were randomly assigned into five groups(n=15): sham operation(group S),group I/R,Dex+I/R(group D),methyllycaconitine +Dex+I/R(group MD),methyllycaconitine +I/R(group M).Methyllycaconitine is an ?7nAChR antagonist,intraperitoneal injection of 40 mg / kg,and other groups received the same volume of saline.Infarct size and the area at risk,serum levels of IL-6,TNF-? and cTnI,mRNA expression of IL-6,TNF-? and HMGB1 in myocardium,protein expression of HMGB1 in myocardium were analyzed by Evans Blue and 2,3,5-triphenyltetrazolium chloride,ELISA,real time quantitative PCR,Western blot and immunohistochemistry respectively.Results Compared with group I/R,the infarct size,the levels of IL-6,TNF-? and cTnI in serum,the mRNA expression of IL-6,TNF-? and HMGB1 and the protein expression of HMGB1 in myocardium were significantly decreased in group D(P<0.05).Compared with group D,the infarct size was significantly increased and those parameters above were significantly increased in group MD(P<0.05).Conclusions Dexmedetomidine preconditioning protects the hearts against ischemia/reperfusion injury in rats by alleviating inflammatory response through ?7nAChR.Part Three: Dexmedetomidine preconditioning attenuates myocardial schemia/reperfusion in rats by regulating the expression of HMGB1 hrough cholinergic anti-inflammatory pathwayObjective To observe whether dexmedetomidine preconditioning can protect the myocardium from ischemia/reperfusion injury by regulating the expression of HMGB1 through cholinergic anti-inflammatory pathway.Methods Sprague Dawley male rats,weighing 230-270 g,were randomly assigned into four groups(n=15): group I/R,Dex+I/R(group D),HMGB1-overexpression+ Dex+I/R(group H),AAV9-blank+Dex+I/R(group B).Infarct size and the area at risk,serum levels of IL-6,TNF-? and cTnI,mRNA expression of IL-6,TNF-? and HMGB1 in myocardium,protein expression of HMGB1 in myocardium were analyzed by Evans Blue and 2,3,5-triphenyltetrazolium chloride,ELISA,real time quantitative PCR,Western blot and immunohistochemistry respectively.Results Compared with group D,the infarct size,the levels of IL-6,TNF-? and cTnI in serum,the mRNA expression of IL-6,TNF-? and HMGB1 and the protein expression of HMGB1 in myocardium were significantly increased in group H(P<0.05).There was no significant difference between group D and group B(P> 0.05)Conclusions Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury in rats by regulating the expression of HMGB1 in the cholinergic anti-inflammatory pathway.