Relationship between failed mechanism of sevoflurane postconditioning-induced myocardial protection and dynamin-related protein 1 activity in diabetic rats

Abstract

Objective To evaluate the relationship between the failed mechanism of sevoflurane postconditioning-induced myocardial protection and the activity of dynamin-related protein 1(Drp1)in diabetic rats. Methods Pathogen-free healthy adult male Sprague-Dawley rats, weighing 220-280 g, in which diabetes mellitus was induced by combination of high-fat and high-sucrose diet and intraperitoneal injection of streptozotoein 30 mg/kg, were studied.Sixty rats with diabetes mellitus were divided into 5 groups(n=12 each)using a random number table: sham operation group(group Sham), myocardial ischemia/reperfusion(I/R)group(group I/R), sevoflurane postconditioning group(group SP), Drp1 inhibitor mitochondrial division inhibitor-1(Mdivi-1)group(group M)and Mdivi-1 plus sevoflurane postconditioning group(group M-SP). Myocardial I/R was induced by occluding the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion except for group Sham.Mdivi-1 1.2 mg/kg was intraperitoneally injected at 15 min before ischemia in M and M-SP groups, and 2.5% sevoflurane was inhaled starting from 5 min of reperfusion in SP and M-SP groups.Blood samples were collected from the right internal jugular vein at 120 min of reperfusion for measurement of serum cardiac troponin I(cTnI)concentrations(by enzyme-linked immunosorbent assay). Rats were then sacrificed and myocardial specimens were obtained for determination of the myocardial infarct size(by TTC), cell apoptosis(by TUNEL), expression of Bax, Bcl-2 and activated caspase-3(by Western blot)and nicotinamide adenine dinucleotide(NAD+ )content(by spectrophotometry). Apoptosis index(AI)and Bax/Bcl-2 ratio were calculated. Results Compared with group Sham, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax/Bcl-2 ratio were significantly increased, the expression of activated caspase-3 was up-regulated, and the NAD+ content was decreased in the other four groups(P 0.05). Compared with group SP, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax/Bcl-2 ratio were significantly decreased, the expression of activated caspase-3 was down-regulated, and the NAD+ content was decreased in group M-SP(P 0.05). Conclusion The failed mechanism of sevoflurane postconditioning-induced myocardial protection may be related to the activity of Drp1 in diabetic rats. Key words: Diabetes mellitus; Myocardial reperfusion injury; Anesthetics, inhalation; Apoptosis