不同HO-1表达水平对糖尿病模型大鼠血管舒张功能及NOS的影响

目的 探讨改变血红素加氧酶-1(HO-1)表达水平对糖尿病(DM)大鼠血管舒张功能的影响及与一氧化氮合酶(NOS)/一氧化氮(NO)的关系.方法 以链脲佐菌素(STZ)诱导DM大鼠模型.SD大鼠分成4组:对照组、DM组、正铁血红素(HO-1诱导剂)组、锌原卟啉(HO-1抑制剂)组.应用离体血管张力检测技术观察胸主动脉舒张功能变化;RT-PCR法及比色法分别检测血管组织和血清中诱生型NOS(iNOS)及内皮型NOS(eNOS)的表达和NO含量.结果 与DM组相比,正铁血红素组血管环对乙酰胆碱舒张百分率有所提高,而锌原卟啉组血管舒张反应继续下降.应用正铁血红素可在提高DM大鼠血管和血清eNOS表达的同时降低iNOS/NO表达;而锌原卟啉组血清中iNOS活性及其在血管组织表达均增高.结论 提高HO-1的表达水平有益于改善DM大鼠血管舒张反应失调,这种保护作用与抑制iNOS/NO的生成、上调eNOS表达水平有关.

Heme oxygenase-1 improves the relaxation function of thoracic aorta in diabetic rats by inhibiting iNOS activity

Objective To investigate the effect of heme oxygenase-1 (HO-1) on vascular endothelium-dependent relaxation response of diabetic rats and the relationship with inducible nitric oxide synthase (iNOS) or endothelial nitric oxide synthase (eNOS). Methods SD rats were rendered diabetic by a single intraperitoneal injection of 50 mg/kg streptozotocin and were divided into four groups: control group, diabetes mellitus group, Hemin (HO-1 inducer) group and ZnPP (HO-1 inhibitor) group. Endothelium-dependent relaxation response to acetylcholine (ACh) was studied in thoracic aortic rings with the isolated artery ring technique. Nitric oxide (NO) production and the activity of iNOS or eNOS in serum were measured. iNOS and eNOS mRNA were detected by RT-PCR. Results Administration with Hemin in diabetic rats could improve vasorelaxation disorder and the cumulative dose responses to ACh (10-7～10-5 mol/L) of Hemin group were increased compared with that of diabetes mellitus group; while treatment with ZnPP in diabetic rats could aggravated the vasorelaxation disturbance. Pretreatment with Hemin in diabetic rats could inhibit the mRNA expression and activity of iNOS and promote those of eNOS, while decreased production of NO was also measured. ZnPP treatment in diabetic rats could enhance iNOS activity but had no effect on eNOS.Conclusions HO-1 could promote eNOS expression,inhibit iNOS activity and decrease NO production in diabetic rats,thus improve the vasodilatation dysfunction of artery.