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

迄今为止，一氧化碳（CO）一直被认为是一种有毒物质。据推测，一氧化碳的毒性是由于它强烈地附着在红细胞中的血红蛋白上，从而导致缺氧。然而，在人体呼气中发现了CO，并且CO是在血红蛋白分解时产生的。1968年，分解血红蛋白的血红蛋白加氧酶（HO）被发现。另一方面，一氧化碳具有血管扩张作用。从与NO的相似性来看，可以推测CO具有细胞内递质的作用。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是HO的诱导亚型。有报道称，HO-1是由氧化应激、缺血/再灌注、炎症等引起的。结果表明，HO-1是近年来在血管硬化部位发现的。为了研究CO在心力衰竭病理生理中的作用，我们对大鼠进行了HO-1诱导实验。接下来，我们尝试制作大鼠心力衰竭模型，并证实一氧化碳的作用。虽然HO-1诱导成功，但未形成心力衰竭模型。有必要建立完全心力衰竭模型。我们对CO的细胞保护作用进行了另一项研究。我们发现CO可以保护离体大鼠心脏线粒体和培养的心肌细胞免受氰化物中毒。

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.