新型光敏剂用于血液病原体灭活的效果与机制研究

Though donor screening and specific testing of blood for transfusion had improved blood safety tremendously, transfusion transmitted infectious diseases (TTIDs) still threaten the blood supply because screening and testing alone cannot exclude all the potential risk from human pathogens due to the existence of window period and emerging of new pathogens. Pathogen removal/inactivation technology, as a proactive and preemptive strategy for the prevention of TTIDs, has been applied successfully to treat blood products and thus compensates for the unideal detection and management during transfusion. Among various pathogen inactivation technologies, photochemical inactivation process that targets nucleic acid of pathogens is the most promising technology which is the only method applied in blood components. Our lab had selected a new photosensitizer YWW007. Preliminary experiment confirmed its inactivated effect is better than Methylene blue and its security had been verified. The damage on nucleic acids of different types of pathogens occurring inside and outside of cells caused by photo-activated phenothiazine dye YWW007 will be studied by analyzing mitochondrial DNA, viral and cellular biomarkers. The relationship between the degree of nucleic acid damage and the efficacy of inactivation will be investigated and the tests will be optimized for pro-inactivation conditions. Results from investigation on the mechanisms of nucleic acid damage by optimizing photoactive phenothiazine dyes may provide basis for developing new pathogen inactivation technology.

尽管通过血液筛查等策略可显著降低其风险,但仍无法避免新发病原体及检测“窗口期”等带来的输血传播疾病风险。血液病原体去除/灭活技术可有效地减少输血传播病原体的风险，可有效弥补输血过程中检测技术和管理手段的不足。其中利用光化学作用灭活病原体是目前唯一可用于血液成分病原体灭活的技术，具有较好应用前景。本实验室前期已筛选出一种新的吩噻嗪类光敏剂YWW007，实验初步证实其灭活效果优越，并已验证其安全性。本研究将进一步对YWW007灭活效果和对血液细胞生理功能的影响进行探索，从而优化其灭活条件，并以线粒体DNA及多种指示病原体和血液细胞为标志物，对YWW007在光照下对游离、胞内及不同类型病原体核酸损伤的情况进行研究，并探索核酸损伤与灭活效果的关系。该研究结果可为研发新的病原体灭活技术提供理论依据和数据支持。

尽管通过血液筛查等策略可显著降低其风险,但仍无法避免新发病原体及检测“窗口期”等带来的输血传播疾病风险。血液病原体去除/灭活技术可有效地减少输血传播病原体的风险，可有效弥补输血过程中检测技术和管理手段的不足。其中利用光化学作用灭活病原体是目前唯一可用于血液成分病原体灭活的技术，具有较好应用前景。本实验室前期已筛选出一种新的吩噻嗪类光敏剂YWW007，实验初步证实其灭活效果优越，并已验证其安全性。在本研究中，我们对YWW007灭活病毒和细菌的效果进行了验证，结果显示，4uM浓度的YWW007对多种指示病毒灭活效果明显，但对血液中的细菌和PPV无有效灭活作用。YWW007可导致红细胞溶血率增加，但在32uM浓度以下，溶血率<1%，YWW007对血小板的数量没有影响，但可刺激部分血小板活化，活化比例约为30%，活化率与光敏剂浓度没有关系，YWW007对凝血因子活性有一定损伤作用，但活性降低在可接受范围。以线粒体DNA及HCV复制子为标志物，对YWW007在光照下对核酸损伤的情况进行研究，发现YWW007对线粒体DNA及HCV核酸均有一定的损伤作用，其灭活效果与和核酸损伤程度存在正相关关系。YWW007在血浆病毒灭活有较好的应用前景，但在红细胞和血小板的应用还需进行进一步探索。