Mitochondrial mechanism of diabetic mellitus-caused abolition of cardioprotection induced by ischemia postconditioning in rats: succinate dehydrogenase / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between the mitochondrial mechanism of diabetic mellitus-caused abolition of cardioprotection induced by ischemia postconditioning (IPO) and succinate dehydrogenase (SDH) in rats.Methods:Thirty-six SPF male non-diabetic Sprague-Dawley rats, aged 16-20 weeks, weighing about 300 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (ND+ Sham group), ischemia-reperfusion (I/R) group (ND+ I/R group) and IPO group (ND+ IPO group). Seventy-two rats with diabetes mellitus were divided into 6 groups ( n=12 each) using a random number table method: sham operation group (DM+ Sham group), I/R group (DM+ I/R group), DM+ IPO group, sham operation+ dimethyl malonate group (group DM+ Sham+ Dme), I/R+ dimethyl malonate group (group DM+ I/R + Dme) and IPO+ dimethyl malonate group (group DM+ IPO+ Dme). The model of cardiopulmonary bypass (CPB) was established, and the model of total I/R injury was induced by ligating the ascending aorta for 30 min followed by 60 min of reperfusion.The animals underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia starting from the onset of reperfusion in each IPO group.In each Dme group, dimethyl malonate was infused through the tail vein at a rate of 4 mg· kg -1·min -1 for 40 min starting from the beginning of CPB.At the end of reperfusion, the myocardial tissues were taken for measurement of mitochondrial respiratory control ratio (RCR) (by the Lufthansa electrode method), mitochondrial membrane potential (MMP) (by the JC-1 method) and the opening of mitochondrial permeability transition pore (mPTP) (by absorptiometry) and for determination of the activity of reactive oxygen species (ROS) (with the fluorescent probe), succinate dehydrogenase (SDH) (using spectrophotometric method) and the contents of succinic acid and fumarate. Results:Compared with ND+ Sham group, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly increased, and MMP, RCR and succinic acid content were decreased in ND+ I/R ( P<0.05). Compared with group ND+ I/R, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly decreased, and MMP, RCR and succinic acid content were increased in ND+ IPO ( P<0.05). Compared with group DM+ Sham, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly increased, and MMP, RCR and succinic acid content were decreased in group DM+ I/R ( P<0.05). Compared with group DM+ I/R, no significant change was found in the parameters mentioned above in group DM+ IPO ( P>0.05). Compared with group DM+ IPO, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly decreased, and MMP, RCR and succinic acid content were increased in group DM+ IPO+ Dme ( P<0.05). Compared with group DM+ I/R+ Dme, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly decreased, and MMP, RCR and succinic acid content were increased in group DM+ IPO+ Dme ( P<0.05). Conclusion:The mitochondrial mechanism of diabetic mellitus-caused abolition of cardioprotection induced by IPO may be related to the enhancement of SDH activity in rats.