摘要
血红素加氧酶（ｈｅｍｅｏｘｙｇｅｎａｓｅ，ＨＯ）是血红素分解代谢过程中的限速酶，它能使细胞内的血红素降解成胆绿素和一氧化碳（ｃａｒｂｏｎｍｏｎｏｘｉｄｅ，ＣＯ）。近来资料表明内源性一氧化碳对生理和病理状态下的血管张力有重要的调节作用。目前尚不清楚内源性ＨＯ／ＣＯ系统是否参与平滑肌细胞增殖过程的调节。本实验在体外培养的大鼠主动脉平滑肌细胞模型上，用血色素加氧酶抑制剂卟啉锌９（ｚｉｎｃｐｒｏｔｏｐｏｒｐｈｙｒｉｎＩＸ，ＺｎＰＰ９）及酶底物血色素左旋赖氨酸盐（ｈｅｍｅＬｌｙｓｉｎａｔｅ，ＨＬＬ）作用于内皮素处理的平滑肌细胞，同时观察细胞ＨＯ活性、ＣＯ产生和释放以及丝裂素活化蛋白激酶（ＭＡＰＫ）活性的变化，以探讨细胞内源性ＨＯ／ＣＯ系统对细胞增殖的调节作用。结果发现：内皮素明显刺激细胞的３ＨＴｄＲ参入，其ＭＡＰＫ活性亦明显增加，同时伴有ＨＯ活性上调和ＣＯ产生释放增加；同时给予ＥＴ１和ＺｎＰＰ９时，ＨＯ活性和ＣＯ的生成释放明显减少，此时３ＨＴｄＲ参入和ＭＡＰＫ活性比单独ＥＴ１组分别增加３１８％（Ｐ＜００１）和３４６％（Ｐ＜００１）；而同时加入ＥＴ１和ＨＬＬ时，ＨＯ活性和ＣＯ生成释放明显?
Heme oxygenase (HO) is a rate limiting enzyme of heme degradation, which converts the cellular heme to bilirubin and carbon monoxide (CO). Recently it is suggested that endogenous CO plays an important role in regulating vascular tone under both physiological and pathological conditions, but it is not clear whether endogenous HO/CO system regulates vascular smooth muscle cells (VSMC) proliferation. In the present study, VMSC ￣ 3H TdR incorporation, mitogen activated protein kinase (MAPK) activity, HO activity and CO release were determined to study the role of endogenous HO/CO system in regulating the VSMC proliferation induced by endothelin 1 (ET 1) in a cultured system. The results showed that ET 1 increased VSMC ￣ 3H TdR incorporation, MAPK activity, HO activity, and CO release were up regulated. Pretreatment of HO inhibitor, zinc protoporphyrin 9 (ZnPP 9), increased the ET 1 induced VSMC ￣ 3H TdR incorporation and MAPK activity by 31 8% and 36 6% ( P <0 01, respectively), whereas pretreatment of heme L lysinate (HLL), a HO substrate, inhibited these activities. This study demonstrated that up regulation of VSMC endogenous HO represents a cellular protective response to stress or injury. Inhibition of HO may enhance VSMC proliferation induced by ET 1 in vitro, a far suggesting that endogenous HO/CO system may be directly involved in the regulation of VSMC proliferation through MAPK signaling pathway.
出处
《生理学报》
CAS
CSCD
北大核心
1999年第3期315-320,共6页
Acta Physiologica Sinica
基金
国家自然科学基金
关键词
血色素加氧酶
一氧化碳
血管平滑肌
内皮素
MAPK
heme oxygenase
carbon monoxide
mitogen activated protein kinase
vascular smooth muscle cell proliferation
