青蒿素联合凉血散血药对脑型疟营血分证脑部血管周细胞的影响

Cerebral malaria is the main cause of death in patients with severe malaria, accounting for more than 80% of the total deaths of malaria. Artemisinin-based drugs can rapidly kill various of malaria parasite in erythrocytic stage, but it can not reduce the damage caused by adhesion and obstruction of infected RBC in the microvessels of the patient's vital organs. Plasmodium has pathogenesis law of the defense-qi-construction and blood pattern in RBC fissiparity stage, which is similar to asexual proliferation cycle in erythrocytic stage. The study intends to establish mouse malaria model with qi-level syndrome and ying-xue syndrome respectively, to dynamically monitor the density and morphology of malaria parasite, and to explore the objective indicators of malaria qi level syndrome and ying-xue syndrome, so as to provide contemporary medical basis for defense-qi-construction and blood pattern identification of malaria. Mouse cerebral malaria model and monkey cerebral malaria model with ying-xue syndrome will be treated with artesunate injection and blood-cooling drugs, in order to explore whether the combination of artemisinin and drugs of cooling and disappearing blood can affect the microvascular diameter and improve microcirculation by regulating the autophagy of pericyte. Through the above experiments, the efficacy of combination treatment can be verified and new ideas of malaria treatment can be provided.

脑型疟是重症疟疾患者致死的主要原因，占疟疾总死亡人数的80%以上。青蒿素类药物能快速杀灭红内期各阶段的疟原虫，但不能减轻重要脏器微血管因含虫红细胞粘附阻塞而带来的损害。疟原虫在红细胞裂殖过程中存在温病卫气营血发病规律，并与红内期无性增殖周期一致。本研究拟构建鼠疟气分证、营血分证模型，动态监测原虫密度和形态，探索气分证、营血分证的客观指标，为疟疾卫气营血辨证提供现代医学依据。鼠脑型疟营血分证模型及猴脑型疟营血分证模型予青蒿琥酯针剂联合凉血散血药物治疗，探讨联合用药是否通过调节脑微血管周细胞的自噬作用，从而影响微血管孔径，改善微循环，验证青蒿素联合凉血散血药治疗脑型疟营血分证的疗效，为疟疾治疗提供新的思路和方法。

脑型疟是导致疟疾病人死亡和神经系统疾病的重要原因，致死率在15%到25%之间，超过25%的幸存者有终身后遗症，具体包括感觉和认知损伤、癫痫和残疾，因此寻求有效的辅助治疗方法为当务之急。.本研究通过构建小鼠实验性脑型疟模型，探索青蒿琥酯联合醒脑静对实验性脑型疟早期干预影响及治疗作用。通过小鼠生存率、小鼠昏迷及行为量表评分、小鼠血脑屏障通透性检测及小鼠脑组织紧密连接蛋白的表达水平检测等，证明青蒿琥酯联合醒脑静的早期治疗能延长感染鼠的生存时间，通过抑制感染鼠脑组织炎症反应，减少疟原虫在脑毛细血管的黏附，保护血脑屏障的完整性。.本研究通过构建猴脑型疟模型，结合中医辨证理论以及临床表现，探索疟疾营血分证的生化指标，为营血分证的诊断提供分子生物学依据，同时观察青蒿琥酯联合醒脑静对营血分证猴脑型疟的疗效，研究发现联合用药组治愈率高于青蒿琥酯组；通过探讨联合用药治疗猴脑疟的分子机制，发现猴脑型疟营血分证模型中猴外周血清sICAM-1等浓度升高，ICAM-1mRNA等在大脑组织中的高水平表达；联合用药组能显著降低猴外周血清sICAM-1等的浓度，下调其在大脑组织中的表达水平，提示其可作为猴脑型疟营血分证分子生物学检测的重要指标。.研究通过构建猴脑型疟模型探索青蒿琥酯联合醒脑静的脑保护作用机制，发现青蒿琥酯联合醒脑静能明显降低猴脑疟模型动物的Glasgow's 昏迷评分，对脑功能起到保护作用，能对自噬和凋亡起到一定的调节，对血脑屏障的完整性起到一定调节，发挥一定的脑保护作用。本研究结果为临床上提高脑型疟患者的生存率和降低脑疟患者的神经损伤提供了新思路。

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