基于HMGB1/PRDXs/NF-κB炎症反应网络研究片仔癀抗缺血性脑卒中的药效物质及作用机制

炎症反应是中风后脑组织损伤的关键环节，高迁移率蛋白B1（HMGB1）、过氧化还原蛋白（PRDXs）、核因子κB（NF-κB）通路与脑缺血后不同时期的炎症反应密切相关。以抗炎作用著称的片仔癀是治疗缺血性脑卒中的有效方剂，前期研究表明片仔癀及其有效成分组具有显著抗脑缺血损伤效应，并且其作用与调控不同炎症反应途径有关。本课题基于脑卒中发病过程中HMGB1/PRDXs/NF-κB炎症反应网络，结合微透析、流式多因子检测、MRI/PET-CT及各种分子生物学技术，从体内外角度及基因、蛋白水平研究片仔癀及其有效成分组对MCAO大鼠脑内HMGB1、PRDXs、NF-κB炎症反应途径中关键蛋白的影响，并借助集群网络分析方法构建可视化特征网络，综合分析片仔癀多成分、多时点、多环节治疗缺血性脑卒中的整体作用及机制，从而在抗炎方面诠释片仔癀治疗缺血性脑卒中的科学内涵，为其临床应用和深入开发奠定基础。

Inflammation response is a key step in the progress of cerebral injury after ischemic stroke. High mobility group protein B1 (HMGB1), peroxiredoxins (PRDXs), and nuclear factor-kappa B (NF-κB) are closely related to the different inflammatory responses during the different period of ischemic stroke. Pien-Tze-Huang (PZH) is a famous traditional Chinese formula , which was effective in treating various inflammatory diseases. Our previous studies have shown that PZH and its active ingredients could significantly inhibit cerebral injury in MCAO rats, which were closely correlated with their anti-inflammatory effects. Therefore, the present project aims to establish a research strategy to investigate the effects of PZH and its active ingredients on the key proteins of different inflammatory signal pathways. In this research strategy, a series of advanced techniques including Microdialysis, Multiple Immunoassays for Flow, MRI/PET-CT, RT-PCR and Western blotting techniques were organically combined. Specifically, the cytokines in the cerebrospinal fluid were measured using Microdialysis and Multiple Immunoassays for Flow techniques, the effects of PZH on the key proteins in the different inflammatory pathways including HMGB1, PRDXs and NF-κB were investigated using RT-PCR and Western blotting, and the improvement of neural functional recovery together with pathologic change such as infarct volume and encephaledema were determined by MRI/PET-CT. Then, according to the cluster network analysis method combining the aforementioned indexes with the concentration of the ingredients in PZH, a visual characteristics network including the effects and the ingredients was built to clarify the action mechanism of PZH based on its anti-inflammation effect. This study provides experimental basis of PZH in treating cerebral ischemic disease, which enrich the function of PZH in clinical application and its deep development.