The mechanism of mitochondrial K (MITO-KATP) channel opening agent in improving myocardial ischemia reperfusion injury in aged CHD rats from the stable effect of mitochondrial membrane
Zhang Haibo
Li Yunli
Ai Jingxue
Gao Rui
Song Zhiming
Abstract：Objective In this study, the mechanism of mitochondrial K (MITO-KATP) channel opening agent in improving myocardial ischemia reperfusion injury in elderly coronary heart disease (CHD) rats were investigated from the stable effect of mitochondrial membrane. Methods Sixty healthy male SD rats (18-20 months) weighing 400-600 g were randomly divided into 3 groups: sham group, model group and nicorandil (Nic) Group, 10 in each group. The model of myocardial ischemia reperfusion (MI/R) in elderly CHD rats was established. Before reperfusion, the Nic group was injected 5 mg/kg into the femoral vein. The sham group and model group were given the same amount of saline. The levels of CK-MB and LDH in serum of the three groups of rats were detected by abdominal aorta blood extraction 24 h after surgery. The changes of mitochondrial membrane potential in rat myocardial cells were measured by flow cytometry. The changes of p-Cx43 protein in the mitochondria of myocardial cells were determined by Western Blot. The protein expressions of Bcl-2 and Bax in myocardial tissue were determined by Western Blot. Results Compared with Sham group, the contents of CK-MB and LDH in serum of rats in the model group were increased (P<0.05), which indicated that myocardial ischemia reperfusion could lead to myocardial cell injury. Compared with the model group, the contents of CK-MB and LDH in serum of rats in Nic group were decreased (P<0.05), which indicated that nicodiltir had an anti-myocardial ischemia effect. Cationic green fluorescent dye rhodamine 123 was used to detect the membrane potential of mitochondria. Compared with Sham group, the myocardial mitochondrial membrane potential of rats in the model group was decreased (P<0.05). However, the myocardial mitochondrial membrane potential was higher in the Nic group than in the model group (P<0.05). This indicated that apoptosis of cardiac cells would lead to the decrease of mitochondrial membrane potential and functional changes, while the mitochondrial K channel opening agent nicodiline could alleviate the mitochondrial damage. Western Blot results showed that compared with sham group, the protein expression of p-Cx43 in the myocardium of rats in the model group was decreased. The protein expression of p-Cx43 in myocardial mitochondria was higher in the Nic group than in the model group, which indicated that nicodiline could up-regulate the protein expression of cardiac mitochondria p-Cx43 and maintain the stability of mitochondria. Compared with Sham group, the protein expression of Bcl-2 in the myocardium tissue of the model group was down-regulated, and the protein expression of Bax was up-regulated. However, the protein expression of Bcl-2 was up-regulated and the protein expression of Bax was down-regulated in myocardial tissues of rats in Nic group, which indicated that mitochondrial K channel opening agent nicodiline could effectively inhibit myocardial apoptosis induced by myocardial ischemia reperfusion. Conclusion Mitochondrial K (MITO-KATP) channel opening agent nicodiline had a protective effect on myocardial ischemia reperfusion injury. The mechanism might be by reducing the contents of serum LDH and CK-MB, maintaining the stability of mitochondrial membrane, and inhibiting the apoptosis of myocardial cells.
Keywords：Mitochondrial K (MITO-KATP) channel openersMyocardial ischemia-reperfusion injuryMitochondrial membrane potentialMyocardial cells
Publication Date：2019-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 560-563,568 )