益气活血法对代谢重编程调节脑出血后血管新生机制的影响研究

项目名称： 益气活血法对代谢重编程调节脑出血后血管新生机制的影响研究

项目编号： No.81473573

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐涛

作者单位： 中南大学

项目金额： 72万元

中文摘要： 代谢是驱动生命活动的根本原因之一。在以往NSFC项目的基础上，本研究从代谢重编程调节血管新生的角度，进一步研究益气活血法促进脑出血（ICH）血管新生的机制。内容：第一部分：运用组织学、分子生物学技术，评价代谢调节蛋白的表达、PI3K/AKT/mTOR/HIF-1 α信号轴在ICH组织的变化；并用侧脑室灌注PI3K抑制剂LY294002，评价信号通路对调节蛋白mRNA、代谢产物的影响。第二部分： Lactate脑组织灌注和LDHA抑制剂阻断ICH后Lactate生成等两种研究策略，评价有氧糖酵解终产物-Lactate对脑内血管新生和血管新生调节信号的影响。第三部分：建立凝血酶诱导脑微ECs增殖模型，阻断Lactate生成，评价Lactate对细胞增殖和血管新生调节信号的影响。意义：通过检测代谢重编程调节血管新生的相关指标，揭示益气活血法促进组织修复，治疗ICH的机制，为该治法研究提供新思路。

中文关键词： 益气活血法；脑出血；代谢重编程；血管新生；乳酸

英文摘要： Metabolism is the basic driving force to life activity.Based on the work of our prevoius NSFC projects,the study is focused on metabolism reprogramming-driven angiogenesis to further elucidate mechanisms of Qi-tonifying and stagnant-eliminating (QTSE) therapy-enhanced angiogensis after intracerebral hemorrhage(ICH). PartI. methods of histology and molecular biology are applied to evaluate expression of metabolism-regulating proteins, changes in PI3K/AKT/mTOR/ HIF-1αaxis; LY294002,PI3K inhibitor,is infused into lateral ventricle to evaluate the effects of the axis on mRNA expression of the regulating proteins.PartII. effect of lactate on angiogenesis and the regulating signal pathways is evaluated by 2 protocols: intracerebral infusion of Lactate, inhibition of Lactate production by LDHA inhibitor.PartIII. lactate production is blocked in proliferating ECs induced by thrombin, to evaluate effect of lactate on ECs proliferation and the regulating signals. By studying the mechanisms related with metabolic reprogramming-driven angiogenesis, we can improve our understanding of QTSE therapy in treating ICH, and provide new ideas for studying the therapy.

英文关键词： Qi-tonifying and stasis eliminating therapy;intracerebral hemorrhage;metabolic reprogramming;angiogenesis;lactate