糖尿病慢性并发症已成为患者致残致死的主要原因。其中多元醇代谢通路的关键限速酶-醛糖还原酶及高血糖引起的组织内氧化应激增加是并发症的重要发病机制。本项目针对糖尿病并发症早期防治药物的活性筛选、体内过程及作用机制研究中对方法学的迫切需求，从体外活性筛选方法及体内过程的活体研究方法入手，以与糖尿病并发症发病机理相关的醛糖还原酶为生物靶分子，兼顾抗氧化及抑制糖基化终末产物生成活性的考察，从临床确有疗效的中药中筛选综合活性好的中药/中药组分。并充分发挥微透析（MD）技术原位取样、无需样品预处理、动态检测等优点，建立微透析-超高效液相色谱/质谱(MD-UPLC/MS)在线联用分析方法，从综合活性好的中药中筛选、表征对醛糖还原酶有抑制活性的成分，并通过对综合活性好的中药中主要成分的体内过程及对相关内源性生物标记物影响的分析，阐明糖尿病并发症防治中药多成分、多靶点的作用机制。

The diabetic complications have become a main reason causing crippledom and death of diabetes patients. The activity of aldose reductase is closely related with the diabetic complications as the key enzyme for limiting the velocity of polyol metabolism pathway. And the increasing of the oxidant stress inside organization, which is caused by hyperglycemia, is an important pathogenesis mechanism of diabetic complications. In this project, for meeting the methodology need of the Chinese medicines for treating diabetic complications, their relevant researches, including the active screening, in vivo process and function mechanism, we will research the methods of in vitro active screening and in vivo process. The screening method of aldose reductase inhibitors(ARIs) will be firstly established and applied to screen ARIs from effective Chinese medicines in clinic use of treating diabetic complications. In order to obtain the Chinese herbs/ component with high comprehensive activities, their anti-oxidant activity and the inhibition activity of advanced glycation end products (AGEs) formation will also be evaluated. With the advantages of in situ sampling, never to need sample pretreatment and dynamic detection etc, microdialysis (MD) technique will combined with ultra performance liquid chromatography/mass spectrometry (LC/MS)technique with the high sensitivity, rapid and selectivity to establish the analytical methods of online MD-LC/MS. The active ingredients as ARIs from the Chinese herbs/ component with high comprehensive activities will be screen and identified by using MD-LC/MS method. And using online MD-LC/MS methods, we will investigate in vivo process of active ingredients from the Chinese herbs/ component with high comprehensive activities and their relevant effects on the content variety of the endogenous biomarkers will also be investigated. These research results will is help to clarify the function mechanism of the multi-components and multi-targets of the Chinese herbal medicine to prevent and treat diabetic complications.