雌激素对高血压人体肠系膜动脉平滑肌细胞大电导钙激活钾通道的作用研究

Effects of estrogen on large-conductance calcium-activated potassium channels of essential hypertension human mesenteric artery smooth muscle cells

目的 研究雌激素（E）对非高血压（NH）及原发性高血压（EH）人体肠系膜动脉平滑肌细胞（HMASMC）大电导钙激活钾通道（BKCa channels）及自发性瞬时外向电流（STOCs）的作用,探讨雌激素在NH及EH下对该通道作用的差异性.方法 急性酶分离法分离获取单个HMASMC,采用全细胞穿孔膜片钳技术记录该细胞上的BKCa和STOCs.结果 雌激素可明显激活NH组HMASMC上的BKCa和STOCs,在测试电压范围内,雌激素使膜电位从0到＋60 mV时BKCa的电流密度均显著性增加,在0和＋60 mV时其电流密度分别从（1.95±0.39）pA/pF、（15.40±4.27）pA/pF增加到（2.81±0.84）pA/pF（P＜0.05,25例）、（26.55±6.24）pA/pF（P＜0.01,25例）,其中0 mV时增加了0.44倍,＋60 mV时增加了0.72倍;电位为-20 mV时STOCs的幅度和频率分别从（7.920±2.031）pA、（3.15±0.79）Hz增加到（12.92±3.41）pA（P＜0.05,25例）、（4.41±0.96）Hz（P＜0.01,25例）,其中幅度增加了0.63倍,频率增加了0.40倍.而EH组在测试的-60到＋50 mV电压范围,雌激素没有这种显著性激活作用,在0和＋60 mV时其电流密度分别从（1.34±0.43）pA/pF、（4.91±1.40）pA/pF增加到（1.53±0.55）pA/pF（P＞0.05,14例）、（8.04±2.0）pA/pF（P＜0.05,14例）,其中0 mV时增加了0.14倍,＋60 mV时增加了0.63倍;在电位为-20 mV时STOCs的幅度和频率分别从（5.39±1.93）pA、（0.75±0.37）Hz增加到（6.70±1.06）pA（P＞0.05,14例）、（2.34±0.98）Hz（P＜0.05,14例）,其中幅度增加了0.24倍,频率增加了2.12倍.结论 雌激素对NH组HMASMC上的BKCa和STOCs有明显的激活作用,而在EH组这种激活作用显著降低,由此推测EH组HMASMC对雌激素的反应性较NH组低,这种差异性将为雌激素合理应用于临床提供有力的实验依据.关键词：高血压;雌激素;人体肠系膜动脉;平滑肌细胞;自发性瞬时外向电流;

Objective To research effect of estrogen on Large-conductance calcium-activated potassium channels and spontaneous transient outward currents of non-hypertension and essential hypertension human mesenteric artery smooth muscle cells, and discuss the variability of two effects. Methods Acute enzyme method was used to isolate human mesentery artery smooth muscle cells and record large-conductance calcium-activated potas- sium channel currents and spontaneous transient outward currents using perforate whole cell patch technique. Resuits Estrogen can obviously active BKCa, and STOCs on HMASMC of NH group. In testing voltage range, estro-gen can obviously increase current density of BKC from 0 to ＋60 mV. At 0 and ＋60 mV, current density of BKCa increased from （1.95±0.39）pA/pF and （15.40±4.27）pA/pF to （2.81±0.84）pA/pF（P〈0.05,n=25）and （26.55± 6.24）pA/pF （P〈0.01 ,n=25 ）. At 0 mV and 60 mV, its current density increase 0.44 and 0.72 times respectively. At -20 mV, amplitude and frequency of STOCs respectively increased from （7.92±2.031）pA and （3.15±0.79）Hz to （12.92±3.41）pA（P〈0.05,n=25）and （4.41±0.96）Hz（P〈0.01 ,n=25）. Its amplitude and frequency added 0.63 and 0AO times. Otherwise, at testing voltage from -60 to ＋50 mV, Estrogen can not active BKc6 and STOCs on HMASMC of EH group. At 0 and ＋60 mV, current density of BKCa increased from （1.34±0.43）pA/pF and （4.91± 1.40 ）pA/pF to （ 1.53 ±0.55 ）pA/pF （P〉0.05, n = 14 ）and （ 8.04 ±2.00 ）pA/pF （P〈0.05, n = 14 ）. Its current density increase 0.14 and 0.63 times respectively. At -20 mV, amplitude and frequency of STOCs respectively increase from （5.39± 1.93 ）pA and （0.75±0.37）Hz to （6.70±1.06 ）pA （P〉0.05, n= 14 ）and （2.34±0.98）Hz （P〈0.05, n = 14）. Its amplitude and frequency increase 0.24 and 2.12 times. Conclusion Estrogen can obviously active BKCa and STOCs on HMASMC of NH group, but this activation is not significant on EH group. We suggest that reaction of estrogen on HMASMC of EH group is lower than NH group. This differentiation will provide the basis of clinical experiments for estrogen reasonable utility.