内源性血红素氧合酶-1/一氧化碳系统对球囊损伤后再狭窄的影响  

Effect of heme oxygenase-1/endogenous carbon monoxide system on restenosis of rabbit carotid artery after balloon injury

作　　者：刘大男[1] 何作云[2] 吴立荣[1] 方颖[1] 刘兴德[1] 李屏[1] 

机构地区：[1]贵阳医学院附属医院心内科,贵州贵阳550004 [2]第三军医大学新桥医院心内科,重庆400037

出　　处：《中国病理生理杂志》2010年第11期2124-2129,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.39800065);贵州省自然科学基金资助项目[No.黔科合字J(2006)2074号];贵州省优秀科技教育人才省长资金资助项目[No.黔省专合字(2007)72号]

摘　　要：目的:探讨血红素氧合酶-1(HO-1)/一氧化碳(CO)系统对球囊损伤后再狭窄的影响及其可能的作用机制。方法:家兔随机分为5组(各组10只):对照组、胆固醇组、血红素组、卟啉锌组和假手术组。对照组予普通饮食,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周后实验组行颈总动脉球囊损伤术,术后继续原喂养给药8周。结果:与对照组比较,胆固醇组颈动脉一氧化氮(NO)生成量、结构型一氧化氮合酶(cNOS)活性显著降低,而CO生成量、HO-1 mRNA和蛋白表达显著增加,内膜面积和内膜/中膜面积比值增大,均P<0.01。与胆固醇组比较,氯化血红素干预显著增高HO-1 mRNA和蛋白表达,增加CO生成量,同时显著降低ET-1 mRNA和蛋白表达,减小内膜面积和内膜/中膜面积比值,均P<0.01;锌原卟啉-9显著降低HO-1 mRNA和蛋白表达,减少CO生成量,而ET-1 mRNA和蛋白表达显著增高,内膜面积和内膜/中膜面积比值增大,均P<0.01。结论:HO-1/CO系统通过代偿和调节NOS/NO系统以及降低ET-1表达,改善内皮功能和抑制内膜增殖,从而有效阻止再狭窄的发生发展。AIM ： To investigate the effect of heine oxygenase - 1 （ HO - 1 ）/carbon monoxide （CO） system on restenosis of carotid artery after balloon angioplasty. METHODS： Fifty rabbits were randomly divided into 5 groups： cantrol group given normal chow （C group）, sham group（Sh group）, 1.5% cholesterol diet group （Ch group）, 1.5% cholesterol diet plus heroin group （Hm group）and zinc protoporphyrin IX group （Zn group）. The experiment lasted for 10 weeks. At the beginning of the 3rd week, the animals in Ch group, Hm group and Zn group underwent balloon injury at one side of common carotid artery. RESULTS： Compared with those in C group, the production of arterial nitric oxide （NO） and activity of constructive nitric oxide synthase （cNOS） were significantly decreased, while CO production and HO -1 expression were significantly increased （all P 〈0. 01 ） in Ch group. Compared with those in Ch group, the arterial CO pro- duction and HO - 1 expression in Hm group were markedly increased, while the expression of endothelin - 1 （ ET - 1 ）, the intimal area and the ratio of intimal area/medial area（I/M） were distinctly reduced. Compared with those in Ch group, the arterial CO production and HO - 1 expression in Zn group were obviously decreased, while the expression of ET - 1, the in- tima area and the ratio of I/M were significantly increased. CONCLUSION： The HO - 1/CO system improves the endothelium function and restrains neointimal proliferation by compensating and regulating NOS/NO system and lowering ET - 1 expression so as to inhibit the restenosis.

关 键 词：球囊损伤 再狭窄 一氧化碳 血红素氧化酶 

分 类 号：R543.5[医药卫生—心血管疾病]