Unité de parasitologie, Unité de recherche sur les maladies infectieuses et transmissibles émergentes - UMR 6236, Institut de recherche biomédicale des armées - antenne de Marseille, Allée du Médecin-colonel Jamot, Parc le Pharo, BP 60109, 13262 Marseille Cedex 7, France.
Malar J. 2012 Jan 10;11:13. doi: 10.1186/1475-2875-11-13.
One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine.
The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining.
AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown.
The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.
疟原虫感染的主要并发症之一是恶性疟疾（CM），每年导致全球有 100 万人死亡，导致长期神经后遗症，且治疗效果仅部分有效。他汀类药物被认为具有免疫调节作用，可减轻脓毒症并具有神经保护作用。阿托伐他汀（AVA）已显示具有体外抗疟活性，并提高了甲氟喹（MQ）和奎宁的活性。
在实验性伯氏疟原虫 ANKA 啮齿动物 CM 模型中，评估了 40mg/kg 腹腔注射 AVA 单独或与 MQ 联合使用的疗效，并根据不同的治疗方案进行了评估。通过 TUNEL 染色评估脑组织病理学变化和神经元凋亡来评估对实验性 CM 的影响。
单独使用 AVA 在治疗方案中对存活率没有影响，但预防性方案中使用 AVA 联合 MQ 而不是单独使用 MQ，导致小鼠死亡明显延迟，并对 CM 症状的发作和寄生虫血症水平有影响。组织病理学发现显示脑损伤与 CM 发作之间存在相关性。未显示 AVA 在 AVA+MQ 联合用药中的神经元抗凋亡作用。
AVA 和 MQ 联合治疗导致小鼠死亡率明显延迟。当药物组合给予小鼠时，在发病、脑型疟疾发作时间和寄生虫血症水平方面存在差异。当与 MQ 联合使用时，AVA 对 P. berghei ANKA 感染小鼠的体内生长抑制和临床结果具有相关作用。
