溶血磷脂酸对心肌细胞胞内钙的影响

Lysophosphatidic acid's effects on intercellular calcium handling of myocardiocytes

目的探讨溶血磷脂酸(LPA)心肌细胞胞内钙的影响。方法分离成年Wistar大鼠的心肌细胞,应用Fluo-4/AM荧光染料,采用逐步钙负荷的方法诱导钙促钙释放。观察不同浓度(0.1、1、5、10、20μmol/L)的LPA对心肌细胞钙促钙释放的影响,并在不同起搏频率(0.25、0.5、1.0 Hz)下观察LPA(10μmol/L)对心肌细胞胞内钙曲线峰值及其变异性的影响。结果 0.1μmol/L的LPA并不影响钙促钙释放次数;从1μmol/L开始及更高浓度(5、10、20μmol/L)可以促进心肌细胞发生钙促钙释放,但这种效应并没有表现出浓度依赖性。同时,LPA(10μmol/L)能显著增加心肌细胞在起搏状态下的胞内钙曲线峰值和0.25、0.5 Hz起搏频率下的变异性。结论 LPA能促进心肌细胞钙促钙释放,并破坏起搏状态下心肌细胞的钙稳态。

Objective To investigate the role of lysophosphatidic acid （LPA） playing in intercellular calcium handling of myocardiocytes. Methods Myocardiocytes were enzymatieally isolated from hearts of adult Wistar rats. They were loaded with fluorescent dye of Fluo-4/AM, which was a fluorescent probe used for measuring intracellular calcium. Step- wise calcium overload was performed to trigger calcium induced calcium release （CICR）. To observe the effects of different concentrations （0.1, 1, 5, 10, 20 μmol/L） of LPA on CICR, and to test whether LPA （ 10 μmol/L） could alter intracel- lular calcium peak and its variability in myocardioeytes paced at different frequencies. Results 0.1 μmol/L of LPA did not alter the frequency of CICR. 1 μmol/L and higher concentrations of LPA （5, 10, 20 μmol/L） promoted CICR in myo- cardiocytes, but such effects of LPA did not show concentration-dependence. Meanwhile, LPA （ 10 μmol/L） significantly increased peaks and the variability of the intracellular calcium curves in paced myocardiocytes. Conclusions LPA pro- moted CICR and destroyed the calcium homeostasis when myocardiocytes are paced.