Department of Infectious Diseases, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Malar J. 2021 Dec 14;20(1):462. doi: 10.1186/s12936-021-03999-2.
Liver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear.
To understand the pathogenesis of liver disease during malaria in pregnancy, comparative proteomic analysis of the liver in a mouse model of malaria in pregnancy was performed.
Decreased levels of mitochondrial and peroxisomal proteins were observed in the livers of pregnant mice infected with the lethal rodent malaria parasite Plasmodium berghei strain NK65. By contrast, increased levels of perilipin-2, amyloid A-1, and interferon (IFN)-γ signalling pathway-related proteins were observed in the livers of infected pregnant mice, suggesting that IFN-γ signalling may contribute to the development of liver disease during malaria in pregnancy. IFN-γ signalling is a potential trigger of inducible nitric oxide synthase (iNOS) expression. Liver disease associated with microvesicular fatty infiltration and elevated liver enzymes in pregnant wild-type mice infected with malaria parasites was improved by iNOS deficiency.
In this study, a causative role of iNOS in liver disease associated with microvesicular fatty infiltration during malaria in pregnancy was demonstrated. These findings provide important insight for understanding the role of iNOS-mediated metabolic responses and the pathogenesis of high-risk liver diseases in pregnancy, such as acute fatty liver.
肝脏疾病是妊娠疟疾的常见特征，但发病机制尚不清楚。
为了了解妊娠疟疾时肝脏疾病的发病机制，对妊娠鼠疟模型的肝脏进行了比较蛋白质组学分析。
感染致死性啮齿动物疟原虫 Plasmodium berghei 株 NK65 的妊娠鼠肝脏中观察到线粒体和过氧化物酶体蛋白水平降低。相比之下，感染妊娠鼠肝脏中发现 perilipin-2、淀粉样蛋白 A-1 和干扰素（IFN）-γ 信号通路相关蛋白水平升高，表明 IFN-γ 信号通路可能导致妊娠疟疾时肝脏疾病的发生。IFN-γ 信号通路是诱导型一氧化氮合酶（iNOS）表达的潜在触发因素。感染疟原虫的野生型妊娠小鼠肝脏疾病伴微泡性脂肪浸润和肝酶升高，iNOS 缺乏可改善。
本研究证明了 iNOS 在妊娠疟疾相关微泡性脂肪浸润性肝病中的致病作用。这些发现为理解 iNOS 介导的代谢反应以及妊娠期间急性脂肪性肝病等高危肝脏疾病的发病机制提供了重要的见解。
