基于中医“毒损脑络”病机，我们前期研究证实了“知母黄柏药对”具有改善糖尿病认知损伤的作用。但该“药对”中皂苷及生物碱类有效成分生物利用度低，难以全面解释其发挥药效的作用途径与机制。鉴于肠道菌群对脑功能的调控作用，我们提出以肠道菌群异常为始动因素，“知母黄柏药对”通过调控肠道菌群改善肠道微生态，缓解机体慢性炎症反应，改善肠道及BBB屏障功能以及减少神经毒性物质等环节，发挥改善糖尿病认知功能障碍作用的工作假说，选择“知母黄柏药对”中生物利用度低的有效成分为代表，采用DNA测序、RT-PCR、免疫组化、Western Blot等方法，考察“知母黄柏药对”基于肠道菌群异常的始动因素，对糖尿病肠道微生态、肠粘膜屏障、BBB完整性、神经毒性物质水平等关键环节的调控作用，揭示其治疗糖尿病认知损伤的作用靶点及机制，进一步丰富中医药从“毒”论治糖尿病脑病的现代科学内涵，为开发防治糖尿病脑病创新中药提供思路。

Based on the pathogenesis theroy of "the injury of brain collaterals by toxins" in Traditional Chinese Medicine (TCM), our previous study have confirmed that Zhimu and Huangbai herb pair (ZBHP) improve diabetes cognitive impairment. However, there is a paradox that the active components of saponins and alkaloids components in ZHHP with low bioavailability, it seemed difficult to explain the pharmacological mechanism. Given the impact of intestinal flora on brain function, this study hypothesis that "the anomaly of gut microbiota is the initial factor, ZHHP improves the intestinal microbiota by regulating intestinal microflora, relieves chronic inflammation, increases the stability of BBB and reduces neurotoxic substances, to play the role of improvement of cognitive dysfunction". The low bioavailability components of ZHHP would be selected, DNA sequencing technology, RT-PCR, immunohistochemistry, Western Blot methods would be employed. The effect of the drugs on the intestinal microbiota, intestinal barrier, BBB integrity and "toxins" levels and other key aspects would be evaluated. To reveal the biological mechanism and targets of ZHHP on treating diabetic cognitive impairment, further enrich modern scientific connotation of TCM on treating diabetes encephalopathy based on the "detoxifying" theropy, and provide a basis for the research on innovative TCM for treating diabetic encephalopathy.