激活SUR2B/Kir6.1通道扩张肺微动脉的分子机制

目的：以ATP敏感性钾通道（K_ATP） SUR2B/Kir6.1亚型开放剂埃他卡林（Ipt）为工具药，研究激活SUR2B/Kir6.1通道扩张肺微动脉作用特征，并探讨其可能的分子机制。方法：利用离体微血管压力-直径监测灌流技术，检测Ipt对大鼠四级肺微动脉的舒张效应（n=6~8），观察内皮损伤后或用K_ATP通道拮抗剂格列苯脲（Gli）、环氧合酶（COX）抑制剂吲哚美辛（Indo）、一氧化氮合酶（NOS）抑制剂L-Nω-硝基精氨酸甲酯（L-NAME）预孵后肺微动脉舒张率的变化。结果：Ipt能够扩张肺微动脉，最大舒张率为（60.53±2.08）%。内皮细胞损伤后，Ipt扩张肺微动脉作用明显减弱，最大舒张率为（9.47±1.56）%，与对照组相比存在显著性差异（P<0.01）。预孵Gli、Indo、L-NAME后，最大舒张率分别下降为（17.49±1.47）%、（37.00±3.88）%、（24.91±2.30）%，与对照组相比均存在显著性差异（P<0.01）。结论：其选择性开放K_ATP通道SUR2B/Kir6.1扩张肺微动脉作用具有内皮细胞依赖性，与其促进内皮细胞释放一氧化氮（NO）和前列环素（PGI₂）相关。

Molecular of pulmonary arterioles relaxation through SUR2B/Kir6.1 channel opening

Objective:To study the dilatation characteristics of ATP-sensitive potassium channel (K_ATP) SUR2B/Kir6.1 subtype opener iptakalim (Ipt) in pulmonary arterioles, and to explore its possible mechanism. Methods:Vessels pressure-diameter monitoring perfusion technique was used to observe the dilatation effects of Ipt in rats fourth pulmonary arterioles (n=6~8). After the pulmonary arterioles were pre-treated with removing endothelium or pre-incubated with K_ATP channel blocker glibenclamide (Gli), cyclo-oxygenase (COX) inhibitor indomethacin (Indo) and nitric oxide synthase (NOS) inhibitor L-Nω-Nitro-arginine methyl ester(L-NAME), the dilatation effects of Ipt were observed. Results:Pulmonary arterioles could be relaxed by Ipt, the maximal relaxation rate was (60.53±2.08)%. Compaired with control group, the effects of Ipt in endothelium denuded arterioles were significantly decreased, the maximal relaxation rate was (9.47±1.56)% (P<0.01). The maximal relaxation rate were decreased to(17.49±1.47)%,(37.00±3.88)% and(24.91±2.30)% respectively after Gli,Indo,L-NAME were pre-incubated (P<0.01). Conclusion:Pulmonary arterioles can be relaxed by Ipt. The selective activation of K_ATP SUR2B/Kir6.1 subtype by Ipt was involved in its mechanisms. The endothelium-dependently dilatation of Ipt was related to nitric oxide (NO) and prostacyclin (PGI₂) released by endothelial cells.