钾流在糖尿病大鼠心室肌细胞的改变机制  

The Alterations of Transient Outward Potassium Currents in Ventricular Myocytes from Diabetic Rats

作　　者：邵阳贞[1] 张代民[1] 李勋[1] 蒋文平[1] 

机构地区：[1]苏州大学附属第一医院心内科,江苏苏州215006

出　　处：《中华高血压杂志》2008年第6期512-515,共4页Chinese Journal of Hypertension

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。Objective To investigate the alterations and molecular mechanism of transient outward potassium currents（Ito） 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 expressions 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 Ito density （＋70 mV） deereased signifieantly in diabetic rats eompared 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 Ito 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 Ito in ventrieular myoeytes in diabetie rats is mainly attributed to the down regulation of gene expressions of ehannel-forming a subunits.

关 键 词：糖尿病 膜片钳 钾通道 心室肌细胞 基因表达 

分 类 号：R587.1[医药卫生—内分泌]