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

作　　者：张利 周梦园 郑丹琳 秦晓玥 李穗敏 曾鹏 邝素娟 杨慧[2,4] 饶芳 邓春玉[1,2,3,4] ZHANG Li;ZHOU Meng-yuan;ZHENG Dan-lin;QIN Xiao-yue;LI Sui-min;ZENG Peng;KUANG Su-juan;YANG Hui;RAO Fang;DENG Chun-yu(School of Biological Science and Engineering,South China University of Technology,Guangzhou 510006,China;Guangdong Provincial Key Laboratory of Clinical Pharmacology,Medical Research Center of Guangdong General Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;School of Medicine,South China University of Technology,Guangzhou 510006,China;Cardiovascular Internal Medicine of Guangdong Cardiovascular Institute,Guangzhou 510100,China)

机构地区：[1]华南理工大学生物科学与工程学院,广东广州510006 [2]广东省人民医院(广东省医学科学院)医学研究部临床药理重点实验室,广东广州510080 [3]华南理工大学医学院,广东广州510006 [4]广东省心血管病研究所心血管内科,广东广州510100

出　　处：《中国药理学通报》2020年第11期1507-1513,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81470440);广东省自然科学基金资助项目(No 2019A1515011933)。

摘　　要：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.

关 键 词：糖尿病小鼠 冠状动脉 血管收缩 L-型钙通道 肌浆网钙释放 钙库操纵性钙通道 

分 类 号：R-332[医药卫生] R322.121