中成药血必净注射液调控重症中暑循环血中单核细胞活性功能和表面分子表达异常的研究

This research is focus on the basic pathogenesis that systemic inflammatory response is induced by enterotoxemia in heat-stroke, equally, it is based on the important pathological mechanism which systemic inflammatory response is initiated by mononuclear cells. A Chinese patent drug, Xuebijing injection is observed and investigated the effect and mechanism of the treatment for severe heat-stroke. In vivo and vitro experiment, the study is performed from multi level such as molecules, cells, animal and clinical.The experiment is aimed to explore the mechanism of Xuebijing injection treating heat-stroke with a core method that visceral injury caused by monocyte excessive activation.The result of investigation is benefit to deepen the understanding of the pathophysiology of severe heat-stroke and verify the role of monocyte excessive activation in the development of severe heat-stroke. Furthermore, it is helpful to reveal the effect and mechanism of Xuebijing injection in treatment of severe heat-stroke. Moreover, it provide theoretical basis and evidence for Xuebijing injection treatment in heat-stroke. The characteristics and advantages of the traditional Chinese Medicine is functioning adequately and explicated by modern medical methods. The eventual objective of this research is increasing the success rate and decreasing mortality and disability in the clinical treatment for severe heat-stroke.

本研究着眼于重症中暑肠源性毒血症引发全身炎症反应的这一根本发病机制，也基于重症中暑单核细胞是全身炎症反应产生的细胞基础这一重要病理机制，观察并探讨中成药血必净注射液对重症中暑的治疗效果和可能机制。通过体内和体外展开实验，从分子、细胞、动物和临床多水平、多个层面进行研究，围绕单核细胞过度活化和脏器损伤为主线，探讨血必净治疗重症中暑的细胞和分子机制。研究结果有利于提高对重症中暑病理生理机制的认识，进一步明确单核细胞活化在重症中暑发生发展中的作用和地位，更有助于揭示血必净治疗重症中暑的作用和机制，为临床开展血必净治疗重症中暑奠定理论基础并充实循证依据，充分发挥祖国中医药学特色和优点，利用现代医学手段进行阐释，最终达到提高临床救治重症中暑成功率，减少因重症中暑所致死亡及伤残的目的。

中暑是我国南方地区常见的季节性疾病，由于临床救治难度大、致死率和致残率高，是困扰危重症医务人员的主要疑难疾病之一。本研究从重症中暑激活单核细胞引发全身炎症反应的这一根本发病机制出发，观察并探讨中成药血必净注射液对重症中暑的治疗效果和可能机制。通过体内和体外展开实验，从分子、细胞、动物和临床多水平、多个层面进行研究，围绕单核细胞过度活化和脏器损伤为主线，探讨血必净治疗重症中暑的细胞和分子机制。. 本课题基本按照既定的研究计划完成相应的实验研究内容。在细胞层面，成功的制备单核细胞的重症中暑模型，检测单核细胞活性功能和表面分子表达的变化，观察单核细胞培养上清刺激下肝细胞的炎症氧化损伤情况，最终发现血必净调控重症中暑诱发的单核细胞活性功能异常并基于此实现对肝细胞损伤的保护性效果。在动物层面，检测重症中暑动物循环血中炎症介质浓度，观察循环血中单核细胞活性功能和表面分子表达变化，以及肝、肺和微循环的炎症氧化损伤情况，发现血必净抑制局部和全身的炎症氧化损伤、调控单核细胞活性功能异常进而对肺、肝和微循环的损伤起保护性作用，最终改善重症中暑动物的预后结局。另外也发现，重症中暑打击肝窦内皮细胞从而诱发肝脏的微循环障碍和炎症性损伤是重症中暑导致肝功能障碍的重要机制。在临床层面，重症中暑可诱发外周血单核细胞HLA-DR表达明显降低，血必净治疗可有效改善其表达异常，进而改善血管内皮细胞损伤。本项目揭示了血必净治疗重症中暑的作用和机制，为临床开展血必净治疗重症中暑奠定理论基础并充实循证依据，所取得成果业绩共获市级和全国学会奖励各1项、国家专利2项，发表SCI论著4篇和中文核心论著1篇，投稿SCI论著2篇（其中1篇接受发表），培养硕士研究生2名。本项目研究成果在广东省内4家三甲医院推广应用，不仅在一定程度上降低重症中暑病死率，更遏制了大部分重症中暑向MODS进展，节约了巨大的医疗资源和社会资源。