Studies on the involvement of carbon monoxide and hem-oxygenase (HO)-1 in the pathophysiology of the heart failure

到目前为止，一氧化碳（CO）一直被认为是一种有毒物质。假设毒性是CO强烈附着在红细胞中的血红蛋白上，并导致缺氧。然而，人们发现，在人的呼气中有CO，并且当血红蛋白分解时产生CO。1968年发现了分解血红蛋白的血红素加氧酶（HO），另一方面，CO具有血管舒张作用。从与NO的相似性来看，推测CO具有作为细胞内递质的作用。随后阐明了CO对细胞凋亡的抑制作用和CO的抗炎作用，表明CO具有细胞毒性和细胞保护作用。HO-1的产生与氧化应激、缺血/再灌注、炎症反应等有关，近年来发现HO-1存在于血管的动脉硬化部位，为了研究CO在心力衰竭病理生理中的作用，本实验对大鼠进行了HO-1的诱导实验。其次，我们尝试建立大鼠心衰模型，并验证一氧化碳的作用。最后，虽然HO-1的诱导成功，但心力衰竭模型未完成。本实验对一氧化碳的细胞保护作用进行了研究，发现一氧化碳能保护离体大鼠心肌线粒体和培养的心肌细胞免受氰化物的损伤。

Up to now, carbon monoxide (CO) has been considered to be a poisoning material. It was assumed the toxicity was for CO to attach strongly to the hemoglobin in the red blood cells, and to cause hypoxia. However, it was found that there was CO in a human expiration, and CO was generated when hemoglobin were decomposed. In 1968 the enzyme hem-oxygenase (HO), which resolves hemoglobin, was discoveredOn the other hand, CO has a vasodilatory effect. From similarity with NO, it is assumed that CO has an action as intracellular transmitter. Afterwards, the inhibition of CO on apoptosis and an anti-inflammatory effects of CO were clarified, and it was shown that CO had both the cell toxicity and the cell protection effect.HO-1 is inducible subtype of HO. It was reported that HO-1 is induced due to oxidative stress, ischemia/reperfusion, inflammation, and so on. It is shown that HO-1 is found in arteriosclerosis part in the vessel recently.To study the participation of CO on pathophysiology of heart failure, we performed the experiment on the HO-1 induction in the rat. Next, we tried to make heart failure model in rat, and to confirm the effect of the carbon monoxide. Finally the heart failure model was not accomplished though the induction of HO-1 succeeded. It is necessary to achieve complete heart failure model.We performed another study on cytoprotective effects of CO. We found that CO protects isolated rat heart mitochondria and cultured cardiomyogenic cells from cyanide poisoning.