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富含 DHA 的鱼油通过控制感染引起的炎症和机械事件,对实验性脑疟疾起到保护作用。

DHA-rich fish oil plays a protective role against experimental cerebral malaria by controlling inflammatory and mechanical events from infection.

机构信息

Department of Parasitology, Microbiology and Immunology and Post-Graduation Program in Biological Science, Research Centre of Parasitology, Federal University of Juiz de Fora, Juiz de Fora, Brazil.

Laboratory of Malaria Research, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.

出版信息

J Nutr Biochem. 2024 Jan;123:109492. doi: 10.1016/j.jnutbio.2023.109492. Epub 2023 Oct 21.

Abstract

Every year, thousands of children, particularly those under 5 years old, die because of cerebral malaria (CM). Following conventional treatment, approximately 25% of surviving individuals have lifelong severe neurocognitive sequelae. Therefore, improved conventional therapies or effective alternative therapies that prevent the severe infection are crucial. Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) are known to have antioxidative and anti-inflammatory effects and protect against diverse neurological disorders, including Alzheimer's and Parkinson's diseases. However, little is known regarding the effects of Ω-3 PUFAs against parasitic infections. In this study, C57BL/6 mice received supplemental treatment of a fish oil rich in the Ω-3 PUFA, docosahexaenoic acid (DHA), which was started 15 days prior to infection with Plasmodium berghei ANKA and was maintained until the end of the study. Animals treated with the highest doses of DHA, 3.0 and 6.0 g/kg body weight, had 60 and 80% chance of survival, respectively, while all nontreated mice died by the 7th day postinfection due to CM. Furthermore, the parasite load during the critical period for CM development (5th to 11th day postinfection) was controlled in treated mice. However, after this period all animals developed high levels of parasitemia until the 20th day of infection. DHA treatment also effectively reduced blood-brain barrier (BBB) damage and brain edema and completely prevented brain hemorrhage and vascular occlusion. A strong anti-inflammatory profile was observed in the brains of DHA-treated mice, as well as, an increased number of neutrophil and reduced number of CD8 T leukocytes in the spleen. Thus, this is the first study to demonstrate that the prophylactic use of DHA-rich fish oil exerts protective effects against experimental CM, reducing the mechanical and immunological events caused by the P. berghei ANKA infection.

摘要

每年都有数千名儿童,尤其是 5 岁以下的儿童,死于脑型疟疾(CM)。经过常规治疗,约 25%的幸存患者存在终身严重神经认知后遗症。因此,改进常规疗法或有效预防严重感染的替代疗法至关重要。ω-3(Ω-3)多不饱和脂肪酸(PUFA)具有抗氧化和抗炎作用,可以预防多种神经疾病,包括阿尔茨海默病和帕金森病。然而,对于 Ω-3 PUFAs 对寄生虫感染的影响知之甚少。在这项研究中,C57BL/6 小鼠在感染疟原虫 ANKA 前 15 天开始接受富含 Ω-3 PUFAs 的鱼油补充治疗,并持续到研究结束。用最高剂量的 DHA(3.0 和 6.0 g/kg 体重)治疗的动物,分别有 60%和 80%的存活机会,而所有未治疗的老鼠都在感染后第 7 天死于 CM。此外,在 CM 发展的关键时期(感染后第 5 天至第 11 天),治疗小鼠中的寄生虫负荷得到控制。然而,在此期间,所有动物都在感染后第 20 天之前发展出高水平的寄生虫血症。DHA 治疗还能有效减轻血脑屏障(BBB)损伤和脑水肿,并完全预防脑出血和血管阻塞。在接受 DHA 治疗的老鼠的大脑中观察到强烈的抗炎谱,以及脾脏中中性粒细胞数量增加和 CD8 T 白细胞数量减少。因此,这是第一项研究表明,预防性使用富含 DHA 的鱼油可对实验性 CM 发挥保护作用,减轻由 P. berghei ANKA 感染引起的机械和免疫事件。

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