脑微血管病变是2型糖尿病（T2DM）常见血管并发症，可导致认知功能障碍。中医认为肾精亏虚、瘀血阻络是该病的核心病机，临床多采用补肾、活血治法，但在药效及药理机制方面尚缺乏明确的实验依据。研究报道LRP-1/RAGE途径介导β淀粉样蛋白(Aβ)在血脑屏障内外转运。Aβ转运异常导致Aβ在脑微血管壁上沉积是诱发DM脑微血管损伤，出现认知功能障碍的主要病理机制之一。前期研究证实补肾法（加味五子衍宗方）可通过抑制Aβ毒性改善认知功能，补肾活血法（加味五子衍宗方加味水蛭）在降血糖同时改善T2DM患者记忆力。本研究以Aβ与脑微血管损伤间的联系为切入点，以整体离体实验研究补肾活血法防治T2DM脑微血管病变，改善认知功能的药效作用；并阐明该作用是否与通过LRP-1/RAGE途径调控Aβ在脑内外的转运有关。本研究将为指导补肾活血治法临床应用提供理论依据，同时为中医药防治糖尿病血管并发症的基础研究开启新的思路。

Diabetic cerebral microangiopathy is a common vascular complication of type 2 diabetes mellitus(T2DM). In Traditional Chinese Medicine, kidney deficiency and damage of essence syndrome and syndrome of static blood obstructing the collateral are regarded to be basic pathogenesis of cognitive impairment caused by diabetic cerebral microangiopathy. Nourishing kidney and activating blood method is commonly used in clinical application, while there is a lack of evidence to prove the efficacy and pharmacological mechanism so far. It is reported that LRP-1/RAGE mediates the internal and external transport of Aβ across blood-brain barrier. Because of its abnormal transport , Aβ deposit at the vessel wall, and attributes to diabetic cerebral microangiopathy, which is a main risk factor for cognitive impairment. Previous researches confirm that modified Wu-Zi-Yan-Zong prescription(MWP), a prescription aiming at nourishing kidney, can improve cognitive impairment and protect neurons by reducing toxicity of Aβ. And further studies show that, Bushen Huoxue prescription(BSHX), in which leech is added based on MWP, can improve T2DM’s memory deterioration syndrome by nourishing kidney and activating blood. In this study, Aβ and cerebral microangiopathy are focused as breakthrough points, and in vivo and in vitro experiments are carried out to study the efficacy of nourishing kidney and activating blood method in improving cognitive impairment by preventing cerebral microangiopathy caused by T2DM. What’s more, the study will declare whether the efficacy is associated with the regulation of LRP-1/RAGE, so as to affect the internal and external transport of Aβ across blood-brain barrier. The study will not only provide theoretical basis for the clinical trial of nourishing kidney and activating blood method, but also pave a way for the basic research on the prevention and treatment of diabetic vascular complications.