缺血性脑血管疾病是中老年人的一种常见病、多发病，是脑卒中发病的主要因素，严重危害人类健康。中药复方制剂在预防和治疗中枢神经系统疾病方面有独特疗效。研究表明，黄连解毒汤预防及治疗脑缺血再灌注损伤时疗效确切。但传统中药汤剂在临床治疗脑血管疾病时具有单次给药剂量大，耐受性差，BBB透过能力低等局限。如何实现黄连解毒汤有效部位的高效包载及靶向治疗是急需解决的问题。本研究拟合成具有高载药量和良好释药特性的介孔硅纳米粒，通过与OX26/ApoE偶联，得到黄连解毒汤有效部位脑靶向介孔硅纳米载体，实现脑部定位治疗，提高药物的脑内生物利用度；采用bEnd.3细胞建立BBB模型，运用Ussing Chamber技术阐明该纳米载体透过BBB的机制；运用PK/PD技术研究该载药体系对脑缺血再灌注损伤的保护作用。本研究将建立一种高载药量、高靶向性的脑部给药系统，为经典复方中药的现代靶向制剂的研究提供新方法和思路。

Ischemic cerebrovascular disease, well known with its high incidence, high death rate, high relapse rate and high mutilation rate, becomes the major pathogenic factor in cerebral apoplexy and causes serious harm to human health. Recent years, compound preparations of Traditional Chinese Medicine (TCM) receive more attentions for their unique effects in preventing and treating central nervous system diseases and lower side effects. The classical prescription Huang-Lian-Jie-Du Decoction is an outstanding representative of them for satisfactory curative effect on treating cerebral ischemia reperfusion injury. However the unneglected limitations of TCM seriously restrict the clinical applications, such as high dosage in single administration, bad patient compliance, low penetration through BBB, and so on. Thus the urgent problem now confronting us is to construct a brain-targeted drug deliver system with high loading capacity and specifically targeted profile loading Huang-Lian-Jie-Du Decoction active fraction. In this study, mesoporous silica nanoparticles (MSNs) with high loading capacity and good drug release profile is coupled with ligands OX26 and ApoE to prepare modified nanoparticles OX26-ApoE-MSNs, which are used for loading Huang-Lian-Jie-Du Decoction active fraction. The OX26-ApoE-MSNs penetrate through BBB by OX26 and ApoE receptor mediated endocytosis and increase the biological utilization rate by accumulating nanoparticles in brain. BBB model is established by brain endothelial cell lines bEnd.3, the penetration mechanism through BBB are investigated by Ussing Chamber experiment, and the pharmacokinetics-pharmacodynamics correlation analysis is applied to evaluate the protecting effect on cerebral ischemia reperfusion injury. By building a brain-targeted drug deliver system with high loading capacity and specifically targeted profile, the research will provide new methods and ideas in the modernization of TCM.