【摘要】 目的研究糖尿病对大鼠心室肌细胞瞬间外向钾流(I_to)的影响及其分子机制,探讨糖尿病引起的心脏损害与心律失常的关系。方法取体质量150～200 g 的雄性 Sprague-Dawley 大鼠,单次腹腔注射链脲菌素（STZ,65 mg/kg,pH=4.5）建立糖尿病大鼠模型,采用酶解法获得单个心室肌细胞,应用膜片钳全细胞方法记录I_to;并用反转录聚合酶链式反应技术进一步半定量编码该电流通道α亚单位基因（Kv4.2、Kv4.3和 Kv1.4）mR-NA 的表达水平。结果与对照组比较,+70 mV 时,糖尿病大鼠心室肌细胞 I_to密度显著降低[对照组:（30.6±3.8）比糖尿病组:（18.9±3.3）pA/pF,P<0.01);半定量分析法显示糖尿病大鼠心室肌细胞 I_to通道α亚单位编码基因 Kv4.2、Kv4.3 mRNA 表达水平分别下调56.9%和46.6%;而 Kv1.4 mRNA 表达则上调约48.0%,3组基因表达水平的改变差异均有统计学意义（P<0.05）。结论糖尿病大鼠心室肌细胞 I_to密度显著降低主要与编码该通道α亚单位的基因表达下调有关。更多还原

【Abstract】 Objective To investigate the alterations and molecular mechanism of transient outward potassi- um currents(I_to) in ventricular myocytes from diabetic rats and explore the mechanism of predisposition of arrhyth- mias in diabetes.Methods The diabetes model was established by a single injection of streptozocin（STZ,65 mg/ kg,pH=4.5） I.P.in male Sprague-Dawley rats with weight 150-200 g.Ventricular myocytes were isolated by enzymatic perfusion.The currents were recorded with the whole-cell patch clamp technique,and gene expres- sions of channel-forming subunits （Kv4.2,Kv4.3 and Kv1.4） were semi-quantified by the technique of reverse transcriptase-polymerase chain reaction（RT-PCR）.Results The I_to density （+70 mV） decreased significantly in diabetic rats compared with controls[control:（30.6±3.8）pA/pF（n=9） vs diabetes:（18.9±3.3）pA/pF（n= 29）（P<0.01）].The gene expression levels of Kv4.2 and Kv4.3 encoding α-subunit of I_to in diabetic rats were markedly decreased in contrast with those of controls by 56.9% and 46.6% respectively,while the level of Kv1.4 mRNA increased by 48.0% in diabetes rats （P<0.01）.Conclusion The decreased density of I_to in ventricular myocytes in diabetic rats is mainly attributed to the down regulation of gene expressions of channel-forming α sub- units.更多还原