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)被认为是一种有毒物质。据推测，这种毒性是因为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存在一氧化碳，当血红蛋白分解时会产生一氧化碳。1968年发现了一种分解血红蛋白的加氧酶(HO)。另一方面，CO具有血管扩张作用。根据与NO的相似性，推测CO具有胞内递质的作用。结果表明，CO具有细胞毒性和细胞保护作用，HO-1是HO的诱导型亚型。据报道，HO-1是由氧化应激、缺血/再灌注、炎症等多种因素诱导的。为了研究CO在心力衰竭的病理生理过程中的作用，我们进行了HO-1诱导大鼠心力衰竭的实验。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，但心力衰竭模型仍未成功。建立完全心力衰竭模型是必要的。我们对CO的细胞保护作用进行了另一项研究。我们发现CO对氰化物中毒的大鼠心肌线粒体和培养的心肌细胞有保护作用。

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.