HO-1通过抑制iNOS改善糖尿病血管舒张功能.doc

HO-1通过抑制iNOS改善糖尿病血管舒张功能.docHO-1通过抑制iNOS改善糖尿病血管舒张功能
邢邯英野战鹰赵晓云凌亦凌1 (河北省人民医院老年医学重点实验室,河北石家庄 050051)
摘要: 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。方法以链脲佐菌素诱导DM大鼠模型。SD大鼠分成4组:对照组、DM组、Hemin(HO-1诱导剂)组、ZnPP(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及内皮型NOS的表达和NO含量。结果与DM组相比,Hemin组血管环对乙酰胆碱舒张百分率有所提高,而ZnPP组血管舒张反应继续下降。应用Hemin可在提高DM大鼠血管和血清内皮型NOS表达的同时降低诱生型NOS/NO表达;而ZnPP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。
关键词: 糖尿病血管并发症;血红素加氧酶-1;一氧化碳;一氧化氮;一氧化氮合酶
基金项目:河北省科技厅指导性计划项目(072761171)
1 河北医科大学病理生理教研室
作者简介:邢邯英,女,邯郸市人,博士,主治医师,主要从事糖尿病血管并发症的分子机制研究。电话:(0311)85988007,E-mail: xinghanying@
中图法分类号: 文献标识码:A
Heme oxygenase-1 improves the relaxation function of thoracic aorta in diabetic rats by inhibiting iNOS activity
XING Han-ying, YE Zhan-ying, ZHAO Xiao-yun, LING Yi-ling.
(Clinical Medical Research Center, Hebei general Hospital, Shijiazhuang 050051, Hebei,China)
Abstract: Objective To investigate the effect of heme oxygenase-1(HO-1) on vascular function of diabetic rats and the relationship with inducible nitric oxide synthase(iNOS) or endothelial nitric oxide synthase(eNOS). Methods SD Rats were divided into four groups: control group, diabetes mellitus(DM) 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. mRNA of iNOS and eNOS was detected by RT-PCR. Results Administration with hemin in diabetic rats could improve vasorelaxation disorder and the curve of cumulative dose responses to ACh (10-8~10–5mol/L) of hemin group shifted pared with that of DM 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, whi