钙感受器STIM1在小鼠主动脉平滑肌收缩反应中的作用研究

目的探讨钙感受器STIM1在小鼠主动脉平滑肌收缩反应中的作用。方法采用Cre-lox重组技术制备平滑肌特异性STIM1敲除小鼠(sm-STIM1-KO);采用离体血管张力测定方法,测定sm-STIM1-KO小鼠主动脉对不同血管收缩剂反应,并给予不同的钙通道阻断剂,观察血管收缩变化。结果sm-STIM1-KO小鼠制备成功。sm-STIM1-KO小鼠钙库操纵的钙通道(SOCC)介导的血管收缩消失;与野生型相比,sm-STIM1-KO小鼠对Phe、5-HT和U46619总的收缩反应无明显变化,但在有钙和无钙的K-H溶液中,经硝苯地平孵育后,两组血管收缩均被抑制,且sm-STIM1-KO小鼠收缩明显低于野生型小鼠(P<0.01);在含硝苯地平的高钾溶液中,Phe引起的快相收缩没有变化,慢相收缩下降(P<0.01);sm-STIM1-KO小鼠肌浆网钙释放介导的血管收缩达峰速度和下降速度明显加快(P<0.05)。结论STIM1是SOCC介导的血管收缩的必须组成成分,且参与肌浆网钙释放介导的血管收缩反应。

Role of Ca2+sensor STIM1 involved in mouse aortic smooth muscle contraction

Aim To investigate the role of Ca 2+sensor STIM1 in mouse aortic smooth muscle contractile response.Methods Smooth muscle-targeted STIM1-knockout(sm-STIM1-KO)mouse was generated by cre-lox technology.The changes of the response to different vasoconstrictors were measured in mouse aorta using a Multi Myograph System.And different Ca 2+channel blockers were given to observe the changes of vasoconstriction.Results The sm-STIM1-KO mice were successfully prepared.Store-operated calcium channel(SOCC)-mediated vasoconstriction disappeared in sm-STIM1-KO mice.Compared with wild-type mice,sm-STIM1-KO mice showed no significant changes in response to Phe,5-HT and U46619.In the K-H solution with and without Ca 2+,vasoconstriction of both groups was inhibited after nifedipine incubation,and vasoconstriction of sm-STIM1-KO was lower than that of wild-type mice(P<0.01).In a 60 mmol·L-1 KCl solution containing nifedipine,the fast phase contraction induced by Phe did not change,but the slow phase contraction decreased significantly(P<0.01).In sm-STIM1-KO mice,peak-reaching and descending rates of vasoconstriction mediated by Ca 2+release from sarcoplasmic reticulum were accelerated(P<0.05).Conclusions STIM1 is an essential component of SOCC-mediated vasoconstriction and is involved in SOCC and sarcoplasmic reticulum Ca 2+release-mediated vasoconstriction.