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首页> 外文期刊>Infection and immunity >Association of Heme Oxygenase 1 with the Restoration of Liver Function after Damage in Murine Malaria by Plasmodium yoelii
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Association of Heme Oxygenase 1 with the Restoration of Liver Function after Damage in Murine Malaria by Plasmodium yoelii

机译：血红素加氧酶1与约氏疟原虫对小鼠疟疾损害后肝功能恢复的关系

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The liver efficiently restores function after damage induced during malarial infection once the parasites are cleared from the blood. However, the molecular events leading to the restoration of liver function after malaria are still obscure. To study this, we developed a suitable model wherein mice infected with Plasmodium yoelii (45% parasitemia) were treated with the antimalarial α/β-arteether to clear parasites from the blood and, subsequently, restoration of liver function was monitored. Liver function tests clearly indicated that complete recovery of liver function occurred after 25 days of parasite clearance. Analyses of proinflammatory gene expression and neutrophil infiltration further indicated that hepatic inflammation, which was induced immediately after parasite clearance from the blood, was gradually reduced. Moreover, the inflammation in the liver after parasite clearance was found to be correlated positively with oxidative stress and hepatocyte apoptosis. We investigated the role of heme oxygenase 1 (HO-1) in the restoration of liver function after malaria because HO-1 normally renders protection against inflammation, oxidative stress, and apoptosis under various pathological conditions. The expression and activity of HO-1 were found to be increased significantly after parasite clearance. We even found that chemical silencing of HO-1 by use of zinc protoporphyrin enhanced inflammation, oxidative stress, hepatocyte apoptosis, and liver injury. In contrast, stimulation of HO-1 by cobalt protoporphyrin alleviated liver inflammation and reduced oxidative stress, hepatocyte apoptosis, and associated tissue injury. Therefore, we propose that selective induction of HO-1 in the liver would be beneficial for the restoration of liver function after parasite clearance.
机译：一旦从血液中清除了寄生虫，肝脏就可以在疟疾感染期间诱导的损伤后有效恢复功能。但是，导致疟疾后肝功能恢复的分子事件仍然不清楚。为了研究这一点，我们开发了一种合适的模型，其中用抗疟疾α/β-蒿醚处理感染了约氏疟原虫（45％寄生虫血症）的小鼠以清除血液中的寄生虫，然后监测肝功能的恢复。肝功能测试清楚地表明，寄生虫清除25天后肝功能完全恢复。对促炎基因表达和中性粒细胞浸润的分析进一步表明，从血液中清除寄生虫后立即引起的肝炎症逐渐减少。此外，发现寄生虫清除后肝脏中的炎症与氧化应激和肝细胞凋亡呈正相关。我们调查了血红素加氧酶1（HO-1）在疟疾后肝功能恢复中的作用，因为HO-1通常在各种病理条件下都可以抵抗炎症，氧化应激和凋亡。发现寄生虫清除后，HO-1的表达和活性显着增加。我们甚至发现通过使用原卟啉锌对HO-1进行化学沉默可增强炎症，氧化应激，肝细胞凋亡和肝损伤。相反，原卟啉钴对HO-1的刺激减轻了肝脏炎症，降低了氧化应激，肝细胞凋亡以及相关的组织损伤。因此，我们建议在肝脏中选择性诱导HO-1将有助于寄生虫清除后恢复肝功能。

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