| Objective:The main reason of high incidence of cardiac arrhythmias,including ventricular fibrillation and sudden death in diabetic patients, probably attributed to myocardial electrophysiology changes, which be induced by the abnormal activity of cadiocyte ion channel after Diabetes mellitus.The transient outward potassium current (Ito) , as the first repolarizing current of myocardium action potential (MAP),plays an important role in action potential shape and duration. Stydies demonstrate that,the changes of Ito density and Ito channel physiological characteristics induced prolongsing platform-stage of MAP and makesing repolarization abnormal. Molecular biology confirmed Ito channel,the channel-forming proteins is encoded by Kv1.4,Kv4.2 and Kv4.3 in rat,Currently.In recent years, considerable evidence suggests disorder of glucolipid metabolism and largely accumulation of metabolic products during fatty acid beta- oxidation,inhibit Ito density and channel expression after diabetes. Trimetazidine (TMZ),the first inhibitor of 3-ketoacyl coenzyme A (CoA) thiolase , inhibited fatty acidβ-oxidation.and did not decrease sedimentary lipid in myocardium, thus took a more safety protective effect of myocardium.However ,none of these studies have reported about the effects of TMZ on the cardiac ion channels of diabetes.Our research aimed to investigate the effects of TMZ on the expressions of Ito density andαsubunit of Ito channel(Kv1.4,Kv4.2,Kv4.3)in the left ventricle of type 2 diabetic rats.Methods:The type 2 diabetic model was established By Feeding high fat diet for a month and single injection of streptozocin 35 mg·Kg-1 peritoneally .Modle rats were randomly divided into treatment group (high-fat diet fed+intragastric administration of TMZ10 mg·Kg-1,modle group (high-fat diet fed+ intragastric administration of normal saline )with each group of 16 rats.Boths group were given relevant drugs once a day for 4 weeKs . The density of transient outward K+ current,Kv1.4,Kv4.2,Kv4.3mRNA and protein levels were detected using real-time polymerase chain reaction (real-time PCR) and Western blot four weeKs laterResults: 1.The density of Ito in left ventricular myocytes of each group:There was no significant difference in membrane capacitance of ventricular myocytes model group[(98.26±23.85)pF(n=10)],treatment group[(106.34±26.42)pF(n=10)]contrast with normal group(113.94±27.16) pF(n=10);The density of Ito(+70mV)in normal control group,model group,treatment group were 20.72±2.93 pA/pF,6.25±1.45 pA/pF ,and 10.62±3.55 pA/pF respectively),compared with the control group,The density of Ito in the model group reduced significantly (p < 0.05),compared with the model group , Ito of treatment group regulated significantly(p < 0.05)。2.The gene expression levels of the pore-forming(α)subunits of Ito in left ventricle of each group:the level of Kv1.4 mRNA in model group (2.01±0.44,n=10)were markedly increased in contrast with those of control group(0.90±0.21,n=10),(P<0.01), and the level of Kv1.4 mRNA in treatment group (1.02±0.38,n=10)were markedly decreased in contrast with model group(P<0.05) ;the expression levels of Kv4.2mRNA(4.42±0.61,n=10),Kv4.3 mRNA(3.53±0.50,n=10)were significantly attenuated when compared with the control group(6.65±0.88.n=10,5.41±0.70 n=10)decrease 33.54% and 34.75% ,respectively, Moreover, in treatment group,the expression of Kv4.2, Kv4.3 gene(5.89±0.52 n=10,4.91±0.57 n=10),were up-regulation 33.26%,39.09%, in compare with model group respectively。The gene expression levels of the pore-forming(α)subunits of Ito were changed, with in treatment group and in control group, but with no statistic significance.3.The expression levels of kv1.4 protein and kv4.2/kv4.3 protein in left ventricle of each group:The expressions of Kv1.4 protein in model group(1.96±0.44,n=10)was significantly increased in compared with control group(0.89±0.25,n=10),but which compared with treatment group ( 1.12±0.28 , n=10 ), the expression levels of Kv4.2 protein (0.42±0.08,n=10),Kv4.3 protein(0.38±0.06,n=10) were significantly attenuated when compared with the control group(0.70±0.12 n=10,0.62±0.09 n=10 ) decrease 40%,38.71% , respectively,Moreover, in treatment group , the expression of Kv4.2 protein,Kv4.3 protein(0.64±0.10,0.58±0.09),were up-regulation, 52.38%,53.63%, in compare with model group respectively;The expressions of Ito channel protein were changed, with in treatment group and in control group, but with no statistic significance;Conclusion:These findings confirm that the amplitude of transient outward K+ current, significantly decreases in the left ventricles myocardium of type 2 diabetic rats, Trimetazidine up-regulate the density of decreasing Ito of . type 2 diabetic rats; the expression of kv1.4 increases significantly,but Kv4.2, Kv4.3 gene and proteins decreases in the left ventricles myocardium of type 2 diabetic rats, Trimetazidine reverse the variance ofαsubunits of Ito channel in the type 2 diabetic rats.
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