内源性一氧化碳在大鼠败血症性休克时低血压发生机制中的作用

应用盲肠结扎法制备大鼠败血症休克模型，研究内源性一氧化碳（ＣＯ）在败血症休克时低血压发病中的作用。用血红素加氧酶（ｈｅｍｅｏｘｙｇｅｎａｓｅ，ＨＯ）抑制剂２，４二甘油次卟啉锌（ｚｉｎｃｄｅｕｔｅｒｏｐｏｒｐｈｙｒｉｎ２，４ｂｉｓｇｌｙｃｏｌ，ＺｎＤＰＢＧ）处理大鼠后，观察动物动脉血压，同时测定主动脉平滑肌组织中ＨＯ活性和ＣＯ生成量。结果发现：败血症大鼠动脉收缩压、舒张压降低，同时血管平滑肌ＨＯ活性和ＣＯ生成明显增加。败血症大鼠用ＺｎＤＰＢＧ处理后，动脉血压明显回升，同时ＨＯ活性和ＣＯ生成明显被抑制。实验表明败血症休克时低血压的发生与血管平滑肌细胞ＨＯ活性增加和内源性ＣＯ生成增多明显相关；应用ＨＯ抑制剂阻断ＨＯ活性能导致内源性ＣＯ生成减少，继而使败血症休克时大鼠血压明显回升。实验提示，内源性ＣＯ对血管张力具有重要的调节作用；ＨＯ活性和内源性ＣＯ生成增加是败血症休克时低血压发生的重要机制之一。

ROLE OF ENDOGENOUS CARBON MONOXIDE IN THE PATHOGENESIS OF HYPOTENSION DURING SEPTIC SHOCK

A sepsis model induced by cecal ligation and puncture was used to study the role of endogenous carbon monoxide in hypotension pathogenesis of rats during septic shock. After administration of zinc deuteroporphyrin 2,4 bisglycol (ZnDPBG), an inhibitor of heme oxygenase (HO), blood pressure (BP), HO activity and carbon monoxide (CO) release from vascular muscle tissue were measured. The results showed that BP of sepsis rats, including systolic and diastolic arterial BP, decreased significantly while HO activity and CO content were significantly increased. In contrast, after administration of ZnDPBG, BP of sepsis rats was significantly increased while the HO activity and CO production were significantly decreased. These findings suggest that HO activity and CO release within vascular musculature are increased during septic shock; inhibition of HO may elevate BP of rats during septic shock through a decrease of endogenous CO production. It is concluded that endogenous CO derived from vascular muscle cells plays an important role in regulating vascular tone, and the up regulation of HO activity followed by subsequent CO production contributes to hypotension pathogenesis during septic shock.