摘要
目的研究17β-雌二醇(E2)对人肠系膜动脉的舒张作用及其机制。方法采用离体血管环灌流的方法,观察E2对内皮完整和去内皮人肠系膜动脉的舒张作用,以及一氧化氮合酶(eNOS)选择性抑制剂N-硝基-L-精氨酸甲酯(L—NAME)、L-NAME+前列环素(PGs)抑制剂吲哚美辛(INDO)、格列本脲(GLY)对这一过程的影响。结果E2(0.5~20.0μmol/L)均可剂量依赖性地舒张人肠系膜动脉;该作用在低水平时内皮完整组明显大于无内皮组(P〈0.01),且在内皮完整组E2的舒张作用可分别被L-NAME、L-NAME+INDO、GLY减弱(P均〈0.01);高水平时去内皮组与内皮完整组E2的舒张比例差异无统计学意义(P〉0.05),在内皮完整组各阻滞剂孵育20min后E2的舒张作用不能被阻断(P均〉0.05)。结论E2对人肠系膜动脉的舒张作用在低水平时具有内皮依赖性,与内皮NO和内皮源性超极化因子(EDHF)的释放、KATP的激活有关,且EDHF比NO更重要;而高水平时的E2舒张人肠系膜动脉是非内皮依赖的,为E2的临床应用提供了重要的实验依据.
Objective To investigate the vaso-relaxing effect of 17β-estrogen on human mesenteric artery (HMA). Methods HMA segments were harvested during large intestine excision surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, smoking habit and estrogen replacement therapy (ERT) were excluded. The vaso-relaxing effects of 17βestradiol on HMA with or without endothelium were examined by 17β-estradiol perfusion in vitro. The influence of NO synthase inhibitor No-nitro-L-arginine methyl ester (L-NAME), L-NAME plus prostaglandin inhibitor indomethacin (INDO), and Glibenclamide (GLY), an ATP-sensitive channel(KATP) blocker were also observed. Results 17β-estradiol caused a concentration-dependent relaxation on HMA. The dose range was from 0.5 (minimal vasodilation) to 20 μmol/L (maximal vasodilation). The vaso-relaxing effect of 17β-estradiol on HMA was endothelium-dependent from 0.5 μmol/L to 5 μmol/L but endothelium-independent from 10 μmol/L to 20 μmol/L. Pretreatment with L-NAME (100 /μmol/L), L-NAME (100 μmol/L) plus INDO (10 μmol/L), and GLY (10 μmol/L) attenuated the 17β-estradiol-induced vasodilation. Conclusions 17β-estradiol results in an endothelium-dependent vaso-relaxation with lower concentration(0. 5 μmol/L to 5 μmol/L) and an endothelium-independent vasodilation with higher concentration(10μmol/L to 20μmol/L).
出处
《中国心血管杂志》
2008年第2期95-98,共4页
Chinese Journal of Cardiovascular Medicine
基金
四川省卫生厅科学研究基金项目(编号:030076)