血红素氧合酶-1和一氧化碳对兔球囊损伤后再狭窄血管的保护作用

目的 研究血红素氧合酶-1(HO-1)与一氧化碳(CO)系统对兔颈动脉球囊损伤后再狭窄血管的保护作用及其可能的机制.方法 新西兰大白兔随机分为5组:对照组、假手术组、胆固醇组、血红素组和卟啉锌组.对照组予普通饲料,其余4组喂饲含1.5%胆固醇饲料,血红素组和卟啉锌组同时分别予氯化血红素或锌原卟啉-9腹腔内注射,2周后行颈总动脉球囊损伤,术后继续原方法喂养给药8周.结果 与对照组比较,胆固醇组颈动脉一氧化氮合酶活性、一氧化氮生成量显著降低,而HO-1表达、CO生成量显著增加(均P＜0.01);与胆固醇组比较,血红素组HO-1表达、CO生成量增加,同时内皮素-1表达降低,内膜厚度和内膜增殖指数最小分别为(442.17±59.14)μm和3.99±0.52与(281.47±21.10)μm和2.49±0.17,均P＜0.01];卟啉锌组HO-1表达、CO生成量降低,而内皮素-1表达增高,内膜厚度和内膜增殖指数最大(698.71±58.37)um和6.17±0.52,均P＜0.01].结论 HO-1与CO系统可能通过代偿和调节一氧化氮合酶和(或)一氧化氮系统以及降低内皮素-1表达,对血管损伤后内皮功能、内膜增生和血管重塑起到保护作用,从而抑制再狭窄.

Abstract：

Objective To investigate the protective effect of heme oxygenase-1 (HO-1)/carbon monoxide (CO) system on restenosis after balloon angioplasty and relative mechanism. Methods Fifty rabbits were randomly divided into 5 groups. Control group received normal chow (Control group), the other rabbits received 1.5% cholesterol diet (Chol group and SH group) or 1.5%cholesterol diet plus hemin (Hem group) or zinc protoporphyrin Ⅸ (Znpp group) for 10 weeks. At the third week of experiment, the three experimental groups underwent balloon injury at one side common carotid artery. Results Compared with control group, arterial nitric oxide production and nitricoxide synthase activity were significantly decreased, while HO-1 expression and CO production were significantly increased (all P＜0. 01 ) in Chol group. The intima thickness and ratio of intima/media (I/M) were lower in Hem group than in Chol group (281.47± 21.10) μm vs. (442.17 ±59.14) μm, 2.49 ± 0. 17 vs. 3.99 ± 0. 52, respectively]. While arterial HO-1 expression and CO production were increased markedly, endothelin-1 expression was distinctly reduced in Hem group group than in Chol group. Compared with Chol group, arterial HO-1 expression and CO production were decreased obviously, while endothelin-1 expression and intima thickness and ratio of intima/media (698.71±58. 37) μm, 6.17±0. 52]were significantly increased in Znpp group (all P＜0. 01).Conclusions The HO-1/CO system plays a protective role on improving endothelium function and restraining neointimal proliferation by compensating and regulating nitricoxide synthase/nitric oxide system and lowering endothelin -1 expression so as to inhibit restenosis after balloon injury.

Protective effect of heme oxygenase-1-endogenous carbon monoxide system on restenosis after balloon injured rabbit carotid artery

Objective To investigate the protective effect of heme oxygenase-1 (HO-1)/carbon monoxide (CO) system on restenosis after balloon angioplasty and relative mechanism. Methods Fifty rabbits were randomly divided into 5 groups. Control group received normal chow (Control group), the other rabbits received 1.5% cholesterol diet (Chol group and SH group) or 1.5%cholesterol diet plus hemin (Hem group) or zinc protoporphyrin Ⅸ (Znpp group) for 10 weeks. At the third week of experiment, the three experimental groups underwent balloon injury at one side common carotid artery. Results Compared with control group, arterial nitric oxide production and nitricoxide synthase activity were significantly decreased, while HO-1 expression and CO production were significantly increased (all P＜0. 01 ) in Chol group. The intima thickness and ratio of intima/media (I/M) were lower in Hem group than in Chol group (281.47± 21.10) μm vs. (442.17 ±59.14) μm, 2.49 ± 0. 17 vs. 3.99 ± 0. 52, respectively]. While arterial HO-1 expression and CO production were increased markedly, endothelin-1 expression was distinctly reduced in Hem group group than in Chol group. Compared with Chol group, arterial HO-1 expression and CO production were decreased obviously, while endothelin-1 expression and intima thickness and ratio of intima/media (698.71±58. 37) μm, 6.17±0. 52]were significantly increased in Znpp group (all P＜0. 01).Conclusions The HO-1/CO system plays a protective role on improving endothelium function and restraining neointimal proliferation by compensating and regulating nitricoxide synthase/nitric oxide system and lowering endothelin -1 expression so as to inhibit restenosis after balloon injury.