猴脑型疟证治规律的研究

Cerebral malaria is one of the dangerous type of malaria which mortality rate as high as 20-50%. Artemisinin drugs can quickly kill the various stages of the malaria parasite within red cells, but can not cure a series of irreversible damage of vital organs, which small blood vessels were blocked by red blood cells that contain insects, so case fatality rate of cerebral malaria remains high. Pathogenesis of cerebral malaria can divided into qiphase and yingfen, xuefen that significantly associated with erythrocyte protozoan schizont. In this study, the relationship between the different phenotypes of qiphase and yingfen, xuefen and protozoan erythrocytic schizont will investigate by animal models of the monkey cerebral malaria. The changes of protozoa density and shape, erythrocyte membrane fluidity, membrane receptors, ion channels and calcium overload will observed, to explore the pathological mechanism of cerebral malaria with qiphase and yingfen, xuefen. To reveal the nature of the pathological process of erythrocyte of cerebral malaria, using white tiger soup which Heat of thirst and Xijiaodihuang soup which clear camp diathermy and cooling blood to stop bleeding joint with artesunate injection for treatment,respectively. To provide new ideas and the right drug for the treatment of cerebral malaria according to the Weifen, qiphase, Yingfen and xuefen.

脑型疟是凶险型疟疾之一，死亡率高达20-50%。青蒿素类药能快速杀灭红内期各阶段的疟原虫，但无法解决脑型疟病人重要脏器微小血管因含虫红细胞粘附阻塞而带来的一系列不可逆损害，导致脑型疟病死率居高不下。脑型疟患者发病机制存在气分和营血分的不同，并与红细胞内原虫裂殖期有相关性。本研究利用猴脑型疟动物模型，探讨猴疟的气分和营血分不同表型和原虫红内裂殖期的关系；动态观察原虫密度和形态、猴含虫红细胞膜流动性、膜表面受体、离子通道和钙超载等方面的变化，探索中医温病气分、营血分证在脑型疟的病理机制；根据卫气营血辨证，探索解除原虫粘附阻塞的中药，分别用清热生津止渴的白虎汤和清营透热、凉血止血的犀角地黄汤，联合青蒿琥酯注射剂进行治疗，从而正确反应和揭示脑型疟红细胞内期的病理过程本质，为脑型疟的治疗提供新的思路和合适的药物。

脑型疟是凶险型疟疾之一，死亡率高达20-50%。很多抗疟药能快速杀灭红内期各阶段的疟原虫，但无法解决脑型疟病人重要脏器微小血管因含虫红细胞黏附阻塞而带来的一系列不可逆损害，导致脑型疟病死率居高不下。脑型疟患者发病机制存在气分和营血分的不同，并与红细胞内原虫裂殖期有相关性。. 本项目利用猴脑型疟动物模型，探讨猴疟的气分和营血分不同表现和原虫红内裂殖期的关系；动态观察原虫密度和形态、猴含虫红细胞膜流动性、钙超载、Na＋-K＋-ATP酶、红细胞骨架和血液流变学等方面的变化，探索中医温病气分、营血分证在脑型疟中的病理机制；根据卫气营血辨证，探索解除原虫粘附阻塞的中药，分别用清热生津止渴的白虎汤和清营透热、凉血止血的犀角地黄汤，联合青蒿琥酯注射剂进行治疗，从而正确反应和揭示脑型疟红细胞内期的病理过程本质，为脑型疟的治疗提供新的思路和合适的药物。. 本项目的主要结论有：.1．猴脑型疟的发生、发展，具有温病卫气营血传变的规律性。.2．青蒿琥酯、青蒿琥酯＋犀角地黄汤、青蒿琥酯＋白虎汤对治疗CM均有不同程度的疗效。其中，青蒿琥酯＋犀角地黄汤组在缩短退热时间和原虫转阴方面有一定优势。.3．青蒿琥酯、青蒿琥酯＋犀角地黄汤、青蒿琥酯＋白虎汤均能减轻CM猴红细胞内钙离子超载。.4．青蒿琥酯、青蒿琥酯＋犀角地黄汤、青蒿琥酯＋白虎汤均能改善CM猴红细胞膜流动性。.5．青蒿琥酯、青蒿琥酯＋犀角地黄汤、青蒿琥酯＋白虎汤均能保护CM猴红细胞膜骨架结构。.6．青蒿琥酯、青蒿琥酯＋犀角地黄汤、青蒿琥酯＋白虎汤均能改善CM猴红细胞膜 Na+-K+-ATP 酶，其中青蒿琥酯+犀角地黄汤组AU值改善最为明显。