Effects Of Glibenclamide,an ATP-sensitive K~+ Channel Blocker,on Cardiac Function In Rats With Ischemic Cardiomyopathy

Objective:To investigate the effect of glibenclamide,an ATP-sensitive K⁺channel blocker,on the structure and function of the heart in rats with ischemic cardiomyopathy.Methods:Thirty-six mature male SD rats（6 weeks of age）were randomly divided into CON group,ICM group and GLI group.The morphology and function of the hearts of the three groups were detected by color Doppler echocardiography.Then,part of the heart tissues were taken for pathological experiments,including HE,Masson and transmission electron microscopy,to observe the pathological conditions of the myocardium in each group.The concentration of Ca²⁺in mitochondria and the permeability of the mitochondrial transition pore in cardiomyocytes were measured.Western blot was used to detect the expression changes of related proteins.Result:Compared with ICM group,the left ventricular end-diastolic diameter of GLI group was increased and EF value decreased significantly in cardiac ultrasound examination 4 weeks after operation.Pathological results（HE,Masson and transmission electron microscopy）showed that gliburide did not alleviate the degree of myocardial injury in rats with ischemic cardiomyopathy,but increased the apoptosis of myocardial cells,and the degree of myocardial injury and myocardial fibrosis in rats was also more serious.The results of Ca²⁺concentration test showed that Ca²⁺overload was significantly increased in GLI group.In the permeability test of mitochondrial conversion pore,the openness of mitochondrial MPTP in GLI group was higher.Western blot results showed that the expressions of mitochondrial fusion protein（OPA-1）and Calumenin were lower in the GLI group,and the expressions of DRP-1 and Cyt C were higher in the GLI group than in the ICM group.Conclusion:The experimental results show that glibenclamide has significant effects on both the structure and the function of the heart in rats.At the same time,glibenclamide aggravated the degree of myocardial injury in rats with ischemic cardiomyopathy,the mechanism of which was related to the specific blocking of mitochondrial KATP channel by glibenclamide.