The Role of Thioredoxin System in Ito Remodeling in Diabetes Rat Hearts / 天津医药

ABSTRACT

Objective To investigate the variation of the thioredoxin system (Trx),and the role of it in transient out-ward potassium current (Ito) channels in left ventricular myocytes of diabetes mellitus (DM) in rats. Methods Forty-five SD rats were divided into DM group and control group. DM group were treated with streptozotocin (STZ) to induce DM model. The values of left ventricular end diastolic diameter (LVEDD), end-systolic diameter (LVESD), fractional shortening (LVFS), ejection fraction (LVEF) and heart rate (HR), QRS duration and corrected QT (QTc) interval were detected by echocardiogra-phy (UCG) and electrocardiogram (ECG) in two groups. The left ventricular myocardial tissue samples were taken to detect the Trx,glutaredoxin (GRX),thioredoxin reductase (TrxR) and glutathione reductase (GR) by using UV spectrophotometer. The level of free thiol (P-SH) of total cardiac protein was detected by 5, 5′-dithio-bis-2-nitrobenzoic acid method. Ito of the cardiomyocytes was recorded by whole-cell patch-clamp method. After being incubated in vitro with insulin(Ins), treated with TrxR inhibitor-auranofin(AF) and 13-cis-retinoic acid(RA), the changes of Ito of the cardiomyocytes were observed. Results Compared with control group, the values of heart rate (HR), left ventricular minor axis decurtaion rate (LVFS), left ventricular ejection fraction (LVEF) and TrxR were lower in DM group. The values of LVEDD, LVESD, QRS and QTc inter-vals, Trx, Grx and P-SH were higher in DM group than those of control group. Ito density was significantly higher in DM+Ins group than that of DM group, Ins+RA group and Ins+AF group when the stimulation voltage ≥ 0 mV (P ＜ 0.05). Conclusion The impaired Trx system in diabetic rat myocardium was the electrophysiological basis of the reduced ventric-ular function and arrhythmia. And Ins was able to reverse the decreased Ito of cardiomyocytes in DM rats.