Diltiazem inhibits cytokine expression in rat myocardium of calcium paradox model / 中国药理学通报

ABSTRACT

Aim To explore the cardiac cytokine expression in rat model of myocardial calcium overload, and the intervention from diltiazem.Methods The intracellular Ca~(2+) overload was induced by the isolated rat heart subjected to 5 min Ca~(2+) depletion and 30 min Ca~(2+) repletion (Ca~(2+) paradox) by the Langendorff technique.There were five groups in this study, including Ca~(2+) overload group, normal control group, Ca~(2+) depletion control group, Ca~(2+) overload-diltiazem group, and Ca~(2+) depletion-diltiazem group.The views of myocardial pathology and ultrastruction were observed by electron microscope and light microscope respectively. The cardiac intracellular [Ca~(2+)]_i was detected by atom spectrophotometer. The expression of TNF-α, IL-1β, L-6, TGF-β1, and IL-10 was detected by RT-PCR method.Results In Ca~(2+) overload group, few inflammatory cells were found in myocardium under the light microscope. And the views of electron microscope presented that cardiocyte membranes, nucleolus, and mitochondria were disorganized obviously.Compared with normal control group, the inflammatory cytokines as TNF-α, IL-1β, and IL-6 were increased significantly whereas there was nearly no difference of the expression of TGF-β1 and IL-10 in Ca~(2+) overload group.Ca~(2+) overload-diltiazem group showed that TNF-α, IL-1β, and IL-6 were decreased significantly. There were no statistical differences in the structure of myocardium, intracellular [Ca~(2+)]_i, and cardiac cytokines expressions in the three control groups, including normal control group, Ca~(2+) depletion control group and Ca~(2+) depletion-diltiazem group.Conclusions Instead of TGF-β1 and IL-10, the expression of TNF-α, IL-1β, and IL-6 is increased obviously in myocardium of calcium paradox model. Diltiazem can inhibit the cardiac expression of TNF-α, IL-1β, and IL-6 induced by myocardial calcium overload.