目的 探讨Kv7通道对人胎盘绒毛膜板动脉(CPAs)血管环舒缩功能的影响及其可能的机制.方法 取内皮完整或去内皮CPAs血管环,分别加入累积浓度递增的XE991、Linopirdine或二甲基亚砜(DMSO),计算收缩率.取去内皮CPAs血管环,经过或者不经过XE991孵育后加入累积浓度递增的U46619,计算收缩率.将去内皮CPAs血管环加入1×10-7 mol/L U46619进行预收缩处理,分别加入累积浓度递增的Kv7通道开放剂[Acrylamide(S)-1、Retigabine、BMS-204352、ML277]及DMSO,计算舒张率.取去内皮CPAs血管环,分别经硝苯地平、levcromakalim及无钙液处理后加入XE991(1×10-5mol/L)或Linopirdine(1×10-4mol/L),计算处理前后收缩率.结果 内皮完整CPAs血管环与去内皮CPAs血管环收缩率随着XE991、Linopirdine浓度的升高而升高,分别于5×10-5、1×10-4mol/L时收缩率最大.与加入同浓度DMSO作用后比较,内皮完整CPAs血管环与去内皮CPAs血管环加入XE991或Linopirdine作用后的收缩率均升高(P均<0.01).内皮完整CPAs血管环与去内皮CPAs血管环加入同浓度XE991或Linopirdine作用后的收缩率比较差异均无统计学意义(P均>0.05).随着U46619浓度的升高,经过或者不经过XE991孵育的去内皮CPAs血管环收缩率均逐渐升高,但经过孵育后升高更明显(P均<0.01).U46619预收缩CPAs血管环加入1×10-4 mol/L Acrylamide(S)-1、Retigabine、BMS-204352作用后的舒张率均高于加入同浓度DMSO(P均<0.01),加入ML277作用后的舒张率无明显变化(P均>0.05).XE991组和Linopirdine组经硝苯地平、levcromakalim及无钙台式液处理后的收缩率均低于处理前(P均<0.01).结论 Kv7通道通过介导细胞膜静息K+电导和静息膜电位的改变而参与调节CPAs血管环的舒缩;阻断Kv7通道可引起CPAs平滑肌细胞去极化,激活L型钙离子通道,引起Ca2+内流和血管收缩.%Objective To study the effects of Kv7 channels on the vasomotor function of human placental chorionic arteries (CPAs).Methods The vascular rings of CPAs with integrated or denuded endothelium were added with the cumulative concentrations of KCNQ channel blockers (XE991 and Linopirdine) or DMSO and we calculated the vasoconstriction.The endothelium-denuded vascular rings of CPAs were added with the cumulative concentrations of U46619 with or without the incubation of XE991, and we calculated the vasoconstriction.The endothelium-denuded vascular rings of CPAs were first treated with U46619 (10-7mol/L), and then were added with the cumulative concentrations of Kv7 channels openers [Acrylamide (S)-1, Retigabine, BMS-204352 and ML277] or DMSO, and we and we calculated the vasoconstriction.The endothelium-denuded vascular rings of CPAs were pretreated with nifedipine, levcromakalim and calcium-free liquid and then were added with XE991(10-5 mol/L) or Linopirdine (10-5 mol/L), at last, we calculated the vasoconstriction before and after treatment.Results The vasoconstrictions of vascular rings of CPAs with integrated or denuded endothelium increased with the increased concentrations of XE991 and Linopirdine (10-8-10-4 mol/L), and the highest vasoconstrictions apperated at 5×10-5 and 10-4 mol/L, which were higher than those treated with the same concentrations of DMSO (all P<0.01).No significant difference was found in the vasoconstriction of vascular rings treated with the same concentration of XE991or Linopirdine between the vascular rings of CPAs with integrated endothelium and vascular rings of CPAs with denuded endothelium (all P>0.05).With the increased concentrations of U46619, the vasoconstriction of endothelium-denuded vascular rings of CPAs with or without the incubation of XE991 increased gradually, and the increase was more significant after the incubation (all P<0.01).Acrylamide (S)-1, Retigabine, and BMS-204352 (10-4 mol/L) relaxed more the U46619-induced contraction of vascular rings of CPAs as compared with that of DMSO (all P<0.01), but ML277 had no effect on U46619-induced relaxation (all P>0.05).The vasoconstriction was lower after treatment of nifedipine, levcromakalim and calcium-free liquid as compared with that before treatment in the XE991 and Linopirdine groups (all P<0.01).Conclusion Kv7 channels (KCNQ) is involved in regulating CPAs tension by mediating the resting cell membrane K+ conductance and static rate of membrane potential changes, and has nothing to do with endothelial integrity.Blocking KCNQ channels can cause the depolarization of vascular smooth muscle cells, activate the L-type calcium channel, and cause calcium ion flow and vasoconstriction.
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