氟灭酸对豚鼠微动脉平滑肌细胞间缝隙连接的抑制作用

Inhibitory effects of flufenamic acid on gap junction of vascular smooth muscle cells in guinea pig

目的探讨氟灭酸(FFA)对微动脉平滑肌细胞间缝隙连接的影响。方法采用全细胞膜片钳技术观察FFA对微动脉段上平滑肌细胞膜电容(Cinput)、膜电导(Ginput)或膜电阻(Rinput)的影响。结果 FFA可以浓度依赖和可逆的降低微动脉段上平滑肌细胞的Cinput和Ginput(或者增加Rinput)。FFA抑制肠系膜动脉(MA)和脑动脉(BA)平滑肌细胞Ginput的IC50分别为56、33μmol/L,微动脉间比较差异无统计学意义(P>0.05)。FFA浓度大于或等于300μmol/L时,MA和BA微动脉段上平滑肌细胞的Cinput、Ginput或Rinput与相应单个平滑肌细胞十分接近。结论 FFA可以浓度依赖和可逆的阻断微动脉平滑肌细胞间缝隙连接,FFA的浓度大于或等于300μmol/L时可以完全阻断微动脉平滑肌细胞间的缝隙连接。FFA对MA和BA微动脉细胞间缝隙连接具有同源性。

Objective To investigate the influence of flufenamic acid （FFA） on gap junction intercellular communication in vascu-lar smooth muscle cells（VSMC） in situ of acutely isolated arteriole segments .Methods Whole-cell patch clamp recordings were used to study the effects of FFA on membrane input capacitance （Cinput ） ,membrane input conductance（Ginput ） or membrane input re-sistance（Rinput ） of VSMCs embedded in arteriole segments .Results FFA concentration-dependently and reversibly suppressed Ginput or increased Rinput ,with an IC50 of 56 and 33μmol/L in acutely isolated mesenteric artery（MA） and brain artery（BA） segments re-spectively .There was not significant difference between MA and BA （P〉 0 .05） .After application of FFA （≥ 300 μmol/L） ,the Cinput ,Ginput and Rinput of the in situ cells were very close to the respective dispersed cell in MA and BA .Conclusion FFA is a reversi-ble gap junction blocker ,achieving a complete electrical isolation of the recorded VSMC at ≥300 μmol/L .FFA suggesting a homo-geneous property of the gap junctions between MA and BA .