The Myocardial Protection By Nicorandil In Rats With Type2Diabetic Cardiomyopathy

Objectives The purpose of this study is to investigate the mechanism of themyocardial protection by nicorandil, an ATP-sensitive potassium channel opener inrats with type2diabetic cardiomyopathy by observing the rat heart weight index,serum oxidation reduction indicators, cardiac enzymes and cardiac diastolic function.Methods The wistar rats were randomly divided into control group（CG）, whichfeed with a normal diet and experimental group（EG）, which feed with high sugar andhigh fat food. Determine the levels of fasting blood glucose, blood lipids and fastinginsulin at the end of4th week in order to detect whether caused by insulin resistanceand dyslipidemia.42rat models with type2diabetic were yielded by feeding withhigh fat and glucose food and injecting streptozotocin（STZ,30mg/kg）. Then the ratswere divided again: control group（CG） which were injected with sodium citrate bufferat the end of6th week and did gavage with normal saline, nicorandil prophylactictreatment group（Nic₁） which were injected with STZ at the end of6th week andtreated by nicorandil （3mg·kg-1·d-1） from the end of4th week to the end of16th week,nicorandil after treatment group （Nic₂） which were injected with STZ at the end of6thweek and treated by nicorandil （3mg·kg-1·d-1） from the end of6th week to the end of 16th week and diabetic cardiomyopathy group（DCM） which were injected with STZat the end of6th weeks and did gavage with normal saline. Determinate the E/A ratioat the end of16th week by echocardiography, before rats in each group weresacrificed. The heart weight index, the activities of blood glucose serum creatinekinase（CK）, lactate dehydrogenase（LDH）, superoxide dismutase（SOD）, the content ofmalondialdehyde（MDA） were determined. The datum obtained were analyzed withSPSS17.0statistical software analysis.Results1. The difference of the fasting blood glucose in DCM, Nic₁and Nic₂group were significant compared with CG group （P<0.05）. The difference in DCM,Nic₁and Nic₂group were not significant（P<0.05）.2. The difference of the heart weight index in DCM, Nic₁and Nic₂group weresignificant compared with CG group （P<0.05）. Compared with DCM group,nicorandil reduced remarkably the heart weight index in Nic₁and Nic₂（P<0.05）. Thedifference of the indication in Nic₁and Nic₂were not significant.3. The difference of the levels of serum creatine kinase（CK） and lactatedehydrogenase（LDH） in DCM group were significant compared with CG group（P<0.05）. Compared with DCM group, there are not significant difference in Nic₁andNic₂with nicorandil. The difference of the indication in Nic₁and Nic₂were notsignificant.4. The activities of SOD were lower significantly in DCM group compared withCG group （P<0.05）. Compared with DCM, nicorandil increased significantly theactivities of serum SOD in Nic₁and Nic₂（P<0.05）. The difference of the indication inNic₁and Nic₂were not significant. The content of MDA were higher significantly inDCM group compared with CG group （P<0.05）. Compared with DCM, nicorandildecreased the content of MDA in Nic₁and Nic₂（P<0.05）. The difference of theindication in Nic₁and Nic₂were not significant.5. E/A ratio increased significantly in DCM group compared with CG group （P<0.05）. Compared with DCM, the E/A can decrease to the normal level in Nic₁andNic₂with nicorandil. The difference of the indication in Nic₁and Nic₂were notsignificant.Conclusions1. Nic_orandil could improve significantly myocardial hypertrophyand diastolic dysfunction of rats with diabetic cardiomyopathy and protectmyocardium from injury.2. Nic_orandil may play myocardial protection by reducing intracellularcalcium overload, inhibiting oxidative stress, reducing myocardial oxidative load anddecreasing cellular energy consumption by opening ATP-sensitive potassiumchannels.