摘要
目的探讨血红素氧合酶1/一氧化碳((HO-1)/CO)系统对兔颈动脉球囊损伤后内膜增殖及内皮功能的影响及其可能的作用机制。方法家兔随机分为对照组、胆固醇组、血红素组、卟啉锌组和假手术组5组,每组10只。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,术后续原喂养给药8周。结果高胆固醇饮食血脂(总胆固醇、甘油三酯、低密度脂蛋白、氧化型低密度脂蛋白)水平显著升高(P<0.01)。与对照组比较,胆固醇组颈动脉一氧化氮生成量、cNOS活性显著降低,而一氧化碳生成量、血红素氧合酶活性显著增加(P均<0.01),内膜面积和内膜/中膜面积比值为(0.586±0.090比1.381±0.180)。与胆固醇组比较,氯化血红素干预显著增加血红素氧合酶活性、一氧化碳生成量,显著降低内皮素1水平,内膜面积和内膜/中膜面积比值最小(0.386±0.076比0.862±0.164;P均<0.01);锌原卟啉9显著抑制血红素氧合酶活性、一氧化碳生成量,显著增高内皮素1水平,内膜面积和内膜/中膜面积比值最大(0.734±0.096比1.843±0.212),差异均有显著性(P<0.01)。结论高胆固醇饮食加球囊损伤严重损害颈动脉NOS/NO系统,血红素氧合酶1/一氧化碳系统通过代偿和调节NOS/NO系统及降低内皮素1表达从而改善内皮功能,抑制血管损伤后内膜增殖和不良重塑。
Aim To investigate the influence of carbon monoxide （CO）/heme oxygenase-1 （HO-1） system on neointimal proliferation and eudothelium function. Methods Fifty rabbits were randomly divided into 5 groups of 10 rabbits. Control group received normal chow（ C group）, the other rabbits received 1.5% cholesterol diet （ Ch group and SH group） or 1.5 % cholesterol diet plus hemin （ Hm group） or zincprotoporphyrin IX （ Zn group） for 10 weeks. At the beginning of 3rth week, Ch group, Hm group and Zn group underwent balloon injury at one side carotid artery. Results High cholesterol diet markedly enhanced the levels of serum TC ,TG, LDLC and ox-LDL （P 〈 0.01 ）. However, they were not much different among these four experimental groups. Compared with control group, arterial NO production and cNOS activity decreased markedly, while CO production and HO activity increased markedly（ all P 〈 0.01 ） , the intima ar- ea and ratio of intima/media （I/M） were respectively 0. 586 ± 0.090 vs 1.381 ± 0. 180 in Ch group. Compared with Ch group, CO production and HO-1 activity increased markedly in Hm group, while in Zn group they were decreased marked- ly. Compared with Ch group, arterial endothelin-1 （ ET-1 ） level of Hm group reduced markedly while in Zn group they were significantly higher than Ch group. The intima area and ratio of I/M were reduced distinctly in Hm group （ respectively 0.386 ±0. 076 vs 0. 862 ±0. 164） while they were distinctly increased in Zn group （ respectively 0.734 ±0.096 vs 1. 843 ±0. 212）. Conclusion Arterial NOS/NO system is impaired significantly in atberosclerotic rabbits induced by highcholesterol diet and balloon injury. HO-1/CO system plays a key role in improving endothelium function and inhibiting neointimal proliferation. This role is related to the reciprocal relationship between HO-1/CO and NOS/NO system in restenosis and the down-regulated expression of ET-1.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2010年第6期345-349,共5页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金资助项目(39800065)
贵州省科学基金资助项目[黔科合字J(2006)2074号]
贵州省优秀科技教育人才省长资金项目[黔省专合字(2007)72号]
关键词
球囊损伤
内膜增殖
内皮功能
一氧化碳
内源性
血红素氧合酶
Balloon Injury
Neointimal Proliferation
Endothelium Function
Carbon Monoxide, Endogenous
Heme Oxygenase
