链脲佐菌素诱导的糖尿病早期小鼠胸主动脉钾通道变化

Changes of potassium channels in thoracic aorta of streptozotocin-induced diabetic mice in early stage

目的 :探讨链脲佐菌素诱导的糖尿病早期小鼠胸主动脉钾通道的变化。方法 :实验采用离体血管的方法测定糖尿病鼠和正常鼠胸主动脉环对血管收缩剂 :6 0mmol/LKCl和苯肾上腺素 (PE)、内皮非依赖性舒张剂 :硝普钠 (SNP)以及电压依赖性钾通道 (KV 通道 ) ,钙激活型钾通道 (KCa通道 ) ,ATP敏感钾通道 (KATP通道 )阻断剂的反应。结果 :糖尿病鼠胸主动脉环对 6 0mmol/LKCl、PE和SNP的效应都显著大于对照组 ;KCa通道阻断剂四乙铵 (TEA)显著降低糖尿病小鼠胸主动脉环在PE的激动下SNP的舒张效应 ,而且其 -logIC50 的差值较对照组显著增大 ;KV 通道阻断剂 4 -氨基吡啶 ( 4 -AP)显著降低糖尿病和正常小鼠胸主动脉环对SNP的舒张效应 ,但是 -logIC50 差值无显著差异 ;KATP通道阻断剂格列苯脲 (Glibenclamide)显著降低糖尿病小鼠胸主动脉环对SNP的舒张效应 ,而对照组无显著阻断作用 ,-logIC50 的差值也无显著差异。结论 :糖尿病早期小鼠胸主动脉平滑肌细胞KCa通道的开放或表达显著增强 。

AIM: To investigate the changes of potassium channels in thoracic aorta of streptozotocin-induced diabetic mouse in the early stage of diabetes mellitus. METHODS: The effects of 60 mmol/L KCl, phenylephrine (PE), sodium nitroprusside (SNP) were measured and concentration-response curves to SNP were determined in the presence and in the absence of the inhibitors of potassium channels on the thoracic aortic rings of diabetic and age-matched control mice in vitro. RESULTS: STZ-diabetic mice showed a significant increase in the maximum contractile response and sensitivity of thoracic aorta to 60 mmol/L KCl and PE. The endothelium-independent relaxation response to SNP was increased by diabetes and were decreased significantly by pretreatment of the vessels with 1 mmol/L tetraethylammonium (TEA), 1 mmol/L 4-aminopyridine (4-AP) and 10 μmol/L glibenclamide in diabetes thoracic aorta. Only 4-AP decreased relaxation response to SNP in age-matched control mice. The -logIC 50 difference of TEA in thoracic aorta rings of diabetes was significantly higher than age-matched control mice.CONCLUSION: In early stage of diabetes mellitus, the opening or expression of K Ca channels is significantly enhanced.The opening of K ATP channels is also enhanced in this stage.