钙调控参与糖尿病小鼠冠状动脉平滑肌收缩变化的机制

Mechanism of Ca^2+ handling involved in coronary arterial constriction change in diabetic mice

目的探讨钙调控参与糖尿病小鼠冠状动脉收缩反应性变化的机制。方法C57BL/6小鼠腹腔注射链脲佐菌素诱导糖尿病模型。通过小血管张力技术,测定收缩剂诱导糖尿病小鼠冠状动脉的张力变化及不同阻断剂对其的影响。结果冠脉的平滑肌收缩主要由经L-型钙通道内流和肌浆网钙释放的钙离子介导,SOC通道不参与其收缩。5-HT和U46619呈浓度依赖性诱导冠脉收缩,与对照组相比,模型组明显减弱(P<0.01);硝苯地平孵育后,5-HT和U46619诱导冠脉的收缩反应均明显减小(P<0.01),且对模型组的抑制幅度明显低于对照组(P<0.01)。在无Ca^2+K-H溶液状态下,硝苯地平孵育后,与对照组相比,模型组对不同收缩剂引发的收缩反应性明显减弱(P<0.01)。高钾刺激模型组冠脉引起的收缩反应明显低于对照组(P<0.01)。结论糖尿病小鼠冠状动脉对血管收缩剂的反应性明显减弱,与L-型钙通道和肌浆网钙释放功能下调有关。

Aim To investigate the mechanism of Ca 2+handling involved in constriction of coronary arteries in diabetic mice.Methods Diabetic model was estab-lished by intraperitoneal injection of streptozotocin into C57BL/6 mice.Coronary artery contractions induced by vasoconstrictors were measured using the Multi Myograph System,and the responses to different blockers were observed in diabetic mice.Results The contraction of coronary artery was mainly mediated by L-type calcium channel and Ca 2+release from the sarcoplasmic reticulum of VSMCs,and the store-operated calcium channel did not mediate it.5-HT and U46619 induced concentration-dependent vasoconstriction in coronary arteries of diabetic mice,and the constrictions elicited by different agonists were markedly reduced compared with control(P<0.01).The vasoconstrictions evoked by 5-HT and U46619 were significantly reduced in coronary artery after incubation with nifedipine.And the inhibition rate of nifedipine on the coronary artery contractile response of diabetic mice was significantly lower than that of wild-type mice(P<0.01).In Ca^2+-free solution containing nifedipine,the responses to different vasoconstrictors in diabetic mice were markedly lower than those in wild-type mice(P<0.01).The high potassium-elicited contractions in diabetic mice significantly decreased compared with control(P<0.01).Conclusions The responses to vasoconstrictors in coronary artery of diabetic mice are significantly reduced,which is associated with the down-regulation of L-type calcium channel and Ca^2+ release from the SR of VSMCs.