内源性一氧化碳对大鼠主动脉球囊损伤后新生内膜形成及丝裂素活化蛋白激酶活性的影响  

The role of endogenous carbon monoxide on neointimal formation and mitogen activated protein kinase activity in aortic artery of rats after balloon injury

作　　者：欧和生[1] 严丽梅[1,2] 杨军[1] 王培勇 庞永正[1] 苏静怡[1] 唐朝枢[1] 

机构地区：[1]北京医科大学第一医院心血管研究所,北京100034 [2]衡阳医学院

出　　处：《北京医科大学学报》1999年第5期404-407,共4页Journal of Peking University(Health Sciences)

基　　金：国家自然科学基金

摘　　要：目的：探讨内源性血红素加氧酶（ｈｅｍｅｏｘｙｇｅｎａｓｅ，ＨＯ）／ 一氧化碳（ｃａｒｂｏｎ ｍｏｎｏｘｉｄｅ，ＣＯ） 系统对大鼠主动脉球囊损伤后新生内膜形成及丝裂素活化蛋白激酶（ｍｉｔｏｇｅｎａｃｔｉｖａｔｅｄ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ， ＭＡＰＫ） 激活的调节作用。方法：采用大鼠主动脉内膜球囊拉伤模型，观察ＨＯ 抑制剂锌卟啉９（ｚｉｎｃ ｐｒｏｔｏｐｏｒｐｈｙｒｉｎＩＸ，ＺｎＰＰ９）或其底物血红素左旋赖氨酸盐（ｈｅｍｅＬｌｙｓｉｎａｔｅ，ＨＬＬ）对血管壁细胞３ＨＴｄＲ掺入和ＭＡＰＫ 活性的影响，同时观察血管平滑肌ＨＯ活性和ＣＯ 生成的变化。结果：内膜拉伤后２ 周血管３ＨＴｄＲ 掺入和ＭＡＰＫ 活性明显增加，同时ＨＯ 活性和ＣＯ 的产生增加；ＺｎＰＰ９ 使血管的３ＨＴｄＲ掺入和ＭＡＰＫ 活性增加更为明显（ 分别比单独拉伤组增加３４ ．６％ 和３９．２％ ，均为Ｐ＜ ０．０１） ；而ＨＬＬ 使血管的３ＨＴｄＲ 掺入和ＭＡＰＫ 活性则明显降低（ 比单独拉伤组分别减少２９．４５ ％ 和３３．６ ％ ，均为Ｐ＜ ０．０１） 。结论：ＨＯ 活性上调或ＣＯ 产生增加是血管对机械拉伤的一种保护性应激反应；内源性ＨＯ／ＣＯObjective: The purpose of this study was to investigate the role of endogenous carbon monoxide (CO) on neointimal formation and mitogen activated protein kinase (MAPK) activity. Methods: On a rat model of aortic endothelium balloon injury. Vascular 3H TdR incorporation, MAPK activity, heme oxygenase (HO) activity and CO release were measured after treatment of ZnPP 9, an HO inhibitor, or heme L lysinate (HLL), an HO substrate. Results: Vascular 3H TdR incorporation and MAPK activity were significantly increased on day 14 after endothelium balloon injury while HO activity and CO release were up regulated. The increased vascular 3H TdR incorporation and MAPK activity after balloon injury could be enhanced by pretreatment of ZnPP 9, whereas they could be inhibited by pretreatment of HLL. Conclusion: HO activity up regulation in aorta was a protective response to balloon injury; endogenous HO/CO system is involved in the regulation of cell proliferation during neointimal formation , and HO induction may become a new clinical approach to prevent cell proliferation in some vascular disease.

关 键 词：HO NO 药理学 MAPK 血管内膜 主动脉球囊损伤 

分 类 号：R654.3[医药卫生—外科学] R972[医药卫生—临床医学]