Changes In Expression Of Cx45 And Cx40 In Sinoatrial Node During Dexmedetomidine-induced Sinus Bradycardia In Rats

Objective:To evaluate the changes in the expression of Cx45 and Cx40 in the sinoatrial node during dexmedetomidine-induced sinus bradycardia in rats;To discuss the mechanism of dexmedetomidine-induced sinus bradycardia in rats;To confirm the association of gap junction proteins with the autonomic nervous system and with sinus chronic arrhythmias.Methods:Eighty clean-grade SPF Sprague-Dawley rats,weighing 250-300 g,were divided into 5 groups?n=16 each?using a random number table method:control group?group C?,low-dose dexmedetomidine group?group D₁?,high-dose dexmedetomidine group?group D₂?,low-dose dexmedetomidine plus atropin group?group D₁A?,and high-dose dexmedetomidine plus atropin group?group D₂A?.Normal saline was intravenously infused in group C.Dexmedetomidine was intravenously infused for 10 min as a loading dose of 20 and 120?g?kg,followed by an infusion of 10 and 60?g·kg^-1·h^-1for110 min in D₁and D₂groups,respectively.In D₁A and D₂A groups,dexmedetomidine was correspondingly given according to the method previously described in D₁and D₂groups,dexmedetomidine was intravenously infused for 10min as a loading dose of 20 and 120?g?kg,and in addition atropin 0.5 mg was intravenously injected at the end of infusing the loading dose of dexmedetomidine,followed by an infusion of 10 and 60?g·kg^-1·h^-1for 110 min.Heat rate?HR?,mean arterial pressure?MAP?and SpO₂were recorded before giving dexmedetomidine and at 10,60 and 120 min after giving dexmedetomidine,and the development of bradycardia was recorded.The sinoatrial node tissues were obtained at the end of administration for determination of the contradistinction between atrial muscle and sinus node tissue,expression of Cx45 and Cx40 protein and mRNA by Masson's trichrome staining,Western blot and real-time polymerase chain reaction,respectively.Results:SpO₂is greater than 90%during the experiment.The incidence of bradycardia was 100%in D₁and D₂groups and 0 after using atropin in D₁A and D₂A groups.In the experimental group,The HR and MAP at 10,60,120 min decreased compared with that before dexmedetomidine administration;In the D₁A and D₂A groups,HR and MAP increased when dexmedetomidine was administered for 60 and 120 minutes compared with dexmedetomidine administration for 10minutes.Compared with group C,HR and MAP were significantly decreased in the other four groups,the expression of Cx45 protein and mRNA was up-regulated,and the expression of Cx40 protein and mRNA was down-regulated in D₁and D₂groups?P<0.05?,and no significant change was found in the expression of Cx45 and Cx40protein and mRNA in D₁A and D₂A groups?P>0.05?.Compared with group D₁,HR and MAP were significantly increased,the expression of Cx45 protein and mRNA was down-regulated,and the expression of Cx40 protein and mRNA was up-regulated in group D₁A?P<0.05?.Compared with group D₂,HR and MAP were significantly increased,the expression of Cx45 protein and mRNA was down-regulated,and the expression of Cx40 protein and mRNA was up-regulated in group D₂A?P<0.05?.Conclusion:The mechanism by which dexmedetomidine induces sinus bradycardia may be related to up-regulated expression of Cx45 and down-regulated expression of Cx40;and the autonomic nervous activity is involved in dexmedetomidine-induced regulation of Cx45 and Cx40 expression in rats;Changes in the expression of gap junction protein may be closely related to the occurrence of sinus chronic arrhythmia.