经 G-蛋白敏感的跨膜信号通路调控心血管肌源性张力

REGULATION OF CARDIOVASCULAR MYOGENIC TONE VIA G PROTEIN SENSITIVE TRANSMEMBRANE SIGNAL PATHWAYS

本研究探讨低氧和ＡｌＦ－４等药物经Ｇ－蛋白敏感的跨膜信号通路对心血管肌源性张力的调控作用。在含有稳定表达Ｎａ＋－Ｃａ２＋交换蛋白的ＣＫ１．４细胞中，用ｆｕｒａ－２荧光影像确定细胞低氧对胞浆游离Ｃａ２＋［Ｃａ２＋］ｉ的影响。在离体犬心乳头肌、颈动脉、主动脉及肺动脉恒温灌流样本中，用张力－电换能器测量低氧灌流和ＡｌＦ－４等药物对心血管肌源性张力的影响。在整体犬体内，按拉丁方设计，用１２５Ｉｓｏｄ－１获得不同剂量ＶＩＳＡ高效剂细胞内分布等药代动力学参数。结果表明：①在ＣＫ１．４细胞中，低氧抑制Ｎａ＋－Ｃａ２＋交换蛋白，产生Ｃａ２＋内流，升高［Ｃａ２＋］ｉ；②低氧灌流削弱ＡｌＦ－４所致的血管收缩而明显易化Ｃａ２＋内流所致的心乳头肌收缩，与结果１）吻合；③ＶＩＳＡ高效剂分布至细胞内，协同ＡｌＦ－４，模拟并激活Ｇ－蛋白敏感的跨膜信号通路，显著改善低氧所致的Ｎａ＋－Ｃａ２＋交换蛋白等跨膜大分子和心血管收缩蛋白氧化损害。

Effects of cellular hypoxia on [Ca 2+ ] i in CK1 4 cells expressed Na + Ca 2+ exchange protein were determined by fura 2 fluorescence imaging. In vitro perfusedof canine cardiovascular samples (37℃),changes of aortic,cervical,pulmonary arterial smooth myogenic tone and cardiac papillary myogenic tone were measured by mechanic electrical transducers via a computer aid autosampling system. In the whole dogs, pharmacolkinetic parameters of a VISA agent at three dosages were calculated by 125 Isod 1 scintillation counting according to a 6×6 statistical model. The results indicated that (① hypoxia inhibited the Na + Ca 2+ exchange protein induced by and elevated Ca 2+ influx and [Ca 2+ ] i in the CK1 4 cells; (② hypoxic perfusions depressed the AlF - 4 activated myogenic vasoconstriction in aortic, cervical and pulmonary arteries,but facilitated the cardiac papillary myogenic contraction Ca 2+ influx induced ,the finding was consistent with the first result; and (③ the VISA agent distributed in the cell together with AlF - 4 simulated and activated G protein sensitive transmembrane sygnal, and signhificantly improved the oxidative injuries of the transmembrane macrowolecules and cardiovascular contraction proteins such as Na + Ca 2+ exchange protein induced by hypoxia.