兔颈总动脉球囊损伤后17β-雌二醇介导iNOS及NO对血管新生内膜增殖抑制的作用

Role of iNOS and NO in 17β-estradiol-mediated inhibition of neointimal formation in rabbit with vascular injury

目的探讨诱导型一氧化氮合酶(iNOS)及一氧化氮(NO)对17β-雌二醇抑制兔颈总动脉球囊损伤反应中新生内膜及中膜增殖的影响。方法在去势雌性兔中建立右颈总动脉球囊损伤模型,实验分为假手术组(sham)、单纯去势组(OVX)、去势后球囊损伤组(OVX+Inj)、去势球囊损伤后补充雌激素组(OVX+Inj+E2)。分别检测各组血管壁新生内膜及中膜的厚度、血浆中NO含量、血管组织中iNOS含量及活性。结果与sham组相比,OVX+Inj组血管组织新生内膜增厚,中膜增生明显,血浆中NO含量及血管组织中iNOS活性降低,E2(estrogen)补充治疗后,可明显增加NO含量及i-NOS活性;western blot结果显示,OVX+Inj组iNOS蛋白表达明显降低,而雌激素替代治疗后iNOS蛋白表达显著增加。结论E2可通过增加血管组织iNOS活性及蛋白表达,促进NO合成,抑制血管损伤后新生内膜及中膜增殖,发挥其血管保护作用。

Objective To investigate the effect of inducible nitric oxide synthase （iNOS） and nitric oxide （NO） on 17β- estradiol-mediated inhibition of neointimal formation in rabbit model with common carotid balloon-injury. Methods Common carotid balloon-injury model was established in ovariectomized rabbits （OVX）. Female New Zealand White rabbits were randomly divided into sham, OVX, OVX ＋ balloon-injury （OVX ＋ Inj）, and OVX ＋ balloon-injury ＋ estradiol supplement （OVX ＋ Inj ＋ E2） groups. The thickness of neointima and tunica media, plasma level of NO, and activity and exprmsion of vascular iNOS were measured. Results Compared with sham group, the thickness of neointima and tunica media increased, but plasma NO level and vascular iNOS activity and expression decreased in OVX ＋ Inj group. The changes of NO and iNOS in OVX ＋ Inj group were reversed by E2 replacement treatment. Conclusion Ee can inhibit the proliferation of neointima and tunica media following balloon-injury via upregulation of iNOS activity and expression and NO production.