目的探讨映山红花总黄酮(TFR)对内皮源性超极化因子(EDHF)介导的全脑缺血再灌注大鼠脑基底动脉(CBA)血管舒张和平滑肌细胞膜静息电位超极化反应的诱导作用。方法采用四血管结扎法建立大鼠全脑缺血再灌注模型,测定离体大鼠CBA平滑肌细胞膜静息电位和血管舒张功能。结果在3×10-5 mol/L L–NAME和1×10-5 mol/L吲哚美辛存在时,全脑缺血再灌注可明显促进乙酰胆碱(Ach,1×10-7～1×10-5 mol/L)诱导大鼠CBA产生非NO、非PGI2介导的血管舒张和平滑肌细胞膜静息电位超极化;TFR 11～2 700 mg/L可使全脑缺血再灌注大鼠CBA产生较明显的非NO、非PGI2介导的血管舒张和平滑肌细胞膜静息电位超极化反应,并能被Ca2+激活的K通道阻断剂四乙胺(TEA,1 mmol/L)和内源性硫化氢(H2S)生成抑制剂dl-炔丙基甘氨酸(PPG,1×10-4 mol/L)显著抑制。结论全脑缺血再灌注明显增强大鼠CBA中非NO、非PGI2介导的血管舒张和平滑肌细胞超级化。TFR明显诱导全脑缺血再灌注大鼠CBA产生此种血管舒张和超级化,即EDHF反应,并可能与H2S有关。

To study the effect of endothelium-derived hyperpolarizing factor (EDHF)-mediated responses of relaxation and hyperpolarization of vascular smooth muscle cell (VSMC) of rat cerebral basilar artery (CBA) subjected to cerebral ischemia/reperfusion (I/R) to total flavones in rhododendra (TFR). Methods The model of global cerebral I/R in rats was made by 4-vessel occlusion (4-VO). The vasodilation and resting membrane potential (RMP) of VSMC of rat CBA were detected in vitro. Results In the presence of 3×10^?5 mol/L Nω-nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of nitric oxide synthase) and 1×10^?5 mol/LIndomethacin (Indo, an inhibitor of PGI2 synthesis), the global cerebral I/R markedly enhanced 1×10?7-1×10^?5 mol/L acetylcholine (Ach)-elicited relaxation and hyperpolarization of RMP of VSMC in rat CBA. In the presence of L–NAME and Indo, 11-2 700 mg/L TFR induced significant and dose-dependent hyperpolarization of RMP of VSMC and relaxation of rat CBA subjected to global cerebral I/R. The hyperpolarization and relaxation were obviously inhibited by tetraethylammonium (an inhibitor of IKCa at 1 mmol/L) and 1×10^?4 mol/L dl-propargylglycine (PPG), an inhibitor of endogenous hydrogen sulfide (H₂S) synthase. Conclusion Global cerebral I/R could enhance the non-NO-non-PGI₂-mediated responses of hyperpolarization and vasorelaxation in rat CAB. In rat CAB subjected to global cerebral I/R, TFR could significantly induce this non-NO-non-PGI₂ hyperpolarization and relaxation, the so-called EDHF response that might be mediated by endogenous H₂S.

国家自然科学基金资助项目(30840104);高等学校博士点专项科研基金资助项目(2007036605)