脑型疟辅助治疗研究进展

Research progress in adjunctive therapy of cerebral malaria

脑型疟是恶性疟原虫感染的主要致死性并发症之一,发病机制尚不完全清楚。但目前的研究多认为,被疟原虫感染的红细胞黏附脑微血管内皮细胞引发的脑部微循环阻塞,以及由此产生的脑血管内皮细胞活化和炎细胞浸润共同导致的免疫病理损伤,协同造成血脑屏障破坏和脑水肿,是脑型疟最主要的发病机制。因此,脑血管内皮细胞活化、受损的程度是决定脑型疟进展、结局的关键因素之一。现有临床研究证明,即便给予积极有效的青蒿素类药物杀虫治疗也不能完全缓解脑型疟症状和可能继发的神经组织损伤,而联用糖皮质激素抗炎治疗副作用大。脑型疟辅助治疗研究涉及其发病机制的多个环节,但由于恶性疟原虫生活史特点和高度抗原变异等诸多因素影响,现有辅助治疗方法均未获预期疗效,亟待探索脑型疟辅助治疗新方法。本文主要以保护脑血管内皮细胞为靶点,从提升内皮细胞的自我保护功能和抑制其他炎细胞或有害因子2个方面对内皮细胞损伤的脑型疟辅助治疗研究进展进行综述。

Cerebral malaria is one of the major fatal complications of Plasmodium falciparum infection,and the pathogenesis is not fully understood.However,most of the current studies believe that the main pathogenesis of cerebral malaria is the obstruction of cerebral microcirculation caused by infected red blood cells adhering to cerebrovascular endothelial cells and the resulting immunopathological damage caused by the activation of cerebrovascular endothelial cells and the infiltration of inflammatory cells,which synergistically result in the disruption of blood⁃brain barrier and brain edema.Therefore,the magnitude of immune activation and damage to the cerebrovascular endothelial cells is one of the key factors in determining the progression and outcome of cerebral malaria.Existing clinical studies have proved that even active and effective anti⁃malarial treatment with artemisinin⁃based drugs cannot completely alleviate the celebral malaria symptoms and the possible subsequent neurological tissue damage,while the combination with anti⁃inflammatory treatment of glucocorticoids may cause serious side effects.The study on combination therapies of cerebral malaria involves multiple links for relevant pathogenesis,while the existing adjunctive therapies have not achieved the expected curative effect due to various factors,such as the complex life cycle and high antigenic variation of P.falciparum.Therefore,new combination therapies are urgently needed.This paper provides a brief review of the current progress in combination therapies against cerebral malaria with the target of protecting cerebrovascular endothelial cells by enhancing the self⁃protection function of endothelial cells and inhibiting the damage of other inflammatory cells or harmful factors to endothelial cells.