Role of zinc transporter Zip1 in cardioprotection of sevoflurane postconditioning in diabetic rats with ischemia and reperfu-sion injury
Objective To explore the correlation between alterations in the expression of the zinc transporter Zip1 during myocardial ischemia-reperfusion in diabetic rats and the cardioprotective effects of sevoflurane postconditioning.Methods Using a random number table,Sprague-Dawley rats were assigned into four groups:myocardial ischemia-reperfusion group(I/R),sevoflurane postconditioning group(I/R+SEV),diabetic myocardial ischemia-reperfusion group(DM+I/R),and diabetic sevoflurane postconditioning group(DM+I/R+SEV),with 15 rats in each group.The myocardial ischemia-reperfusion injury model was simulated by 30 min ischemia and 120 min reperfusion.The rats were intraperitoneally injected with STZ at a dosage of 35 mg/kg after feeding a high-fat,high-sugar diet for eight weeks,and then given 30 min ischemia and 120 min reperfusion in DM+I/R group and DM+I/R+SEV group.The rats in I/R+SEV group and DM+I/R+SEV group inhaled 2.5％sevoflurane for 10 min via vaporizer from one minute prior to reperfusion.Serum cardiac troponin Ⅰ(cTnⅠ)concentration was determined using ELISA.Then the rats were executed to collect hearts.Myocardial infarction area was assessed by TTC staining,and Zip1 protein expression was evaluated by immunohistochemistry.Additionally,the expression levels of myocardial Zip1,Drp1,PINK1,and Parkin proteins were detected by Western blotting.Results Compared to I/R group,serum cTnⅠ level and myocardial infarction volume percentage were decreased(P＜0.05),Zip1 expression showed no significant change(P＞0.05),and the expressions of Drp1,PINK1,and Parkin proteins were reduced(P＜0.05).Compared to I/R group,serum cTnⅠ level and myocardial infarction volume percentage were increased in DM+I/R group(P＜0.05),Zip1 expression was reduced(P＜0.01),Drp1 expression was elevated(P＜0.05),and PINK1 and Parkin expressions were significantly decreased(P＜0.01).Compared with I/R+SEV group,serum cTnⅠ level and myocardial infarction volume percentage were increased in DM+I/R+SEV group(P＜0.05),Zip1 expression was decreased(P＜0.01),Drp1 expression was significantly increased(P＜0.01),and PINK1 and Parkin expressions were reduced(P＜0.05).There were no statistically significant differences in the above indexes between DM+I/R group and DM+I/R+SEV group(P＞0.05).Conclusion The loss of cardioprotective effects after sevoflurane postconditioning in diabetic rats may be associated with the downregulation of myocardial Zip1 expression.
Zinc transporter Zip 1ischemia-reperfusion injuryautophagysevoflurane postconditioningdiabetes mellitus
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