羟基红花黄色素A抑制人源化脓毒症小鼠外周血CD4+T淋巴细胞凋亡的作用及机制研究

项目名称： 羟基红花黄色素A抑制人源化脓毒症小鼠外周血CD4+T淋巴细胞凋亡的作用及机制研究

项目编号： No.81503320

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王金平

作者单位： 深圳大学

项目金额： 18万元

中文摘要： 阻止CD4+T淋巴细胞过度凋亡治疗脓毒症时的免疫抑制是目前研究的热点。血必净注射液是国际上唯一纯中药治疗脓毒症的药物，其主要有效成分羟基红花黄色素A（HSYA）可通过线粒体损伤途径抑制细胞凋亡，然HSYA是否可通过阻止CD4+T淋巴细胞过度凋亡抗脓毒症？尚有待阐明。本项目基于前期对血必净注射液治疗脓毒症作用机制的研究基础，拟在联合免疫缺陷小鼠移体内移植人CD34+细胞，鉴定小鼠体内成功建立人的免疫系统后，应用盲肠结扎穿孔法制备人源化脓毒症小鼠模型，研究HSYA对外周血CD4+T淋巴细胞凋亡及线粒体损伤通路各凋亡因子基因和蛋白表达的影响，分析HSYA对脓毒症的治疗作用及机制，在体外细胞模型，深入观察HSYA对CD4+T淋巴细胞凋亡线粒体损伤途径的影响。确证脓毒症时HSYA通过线粒体损伤途径抑制外周血CD4+T淋巴细胞凋亡治疗脓毒症的作用机制，筛选药物作用靶点。

中文关键词： 脓毒症；淋巴细胞；细胞凋亡；线粒体；羟基红花黄色素A

英文摘要： The immunosuppression effect has become great concern when treating sepsis via preventing CD4+ lymphocytes excessive apoptosis.The possibility of treating immune suppression of sepsis through inhibiting excessive CD4+T lymphocyte apoptosis has become a widely concern.The only traditional Chinese medicine for sepsis therapy, Xuebijing injection consists mainly hydroxysafflor yellow A (HSYA), which can inhibit apoptosis via mitochondrial damage. Howere，It remains to be demonstrated that whether HSYA can treat sepsis via inhibition of abnormal CD4+ T lymphocyte apoptosis. Our previous studies have explored the underlying mechanisms of the treatment effect of Xuebijing injection on sepsis. we aim to establish the human immune system in the combined immunodeficiency mice by transplanting the human CD34+ cells to the mice.Through cecal ligation and puncture, we will model the human source pyogenic sepsis in mice. We aim to study the impact of HSYA on the relevant apoptosis genes and proteins expression of peripheral blood of inflammatory cytokines, CD4+T lymphocytes apoptosis, and the mitochondrial damage. By inhibiting different path way of apoptosis respectively in vivo study, we will further our understanding of the effect of HSYA on the mitochondrial damage of CD4+T lymphocytes. We aim to find the drug targets by verifying the mechanisms of inhibition effect of HYSA on peripheral blood of CD4+T lymphocytes apoptosis via mitochondrial damage.

英文关键词： sepsis;lymphocyte;apoptosis;mitochondria;hydroxysafflor yellow A