本研究基于荟萃法探讨了核桃仁干预2型糖尿病的作用机制。采用TCMSP数据库筛选核桃仁的主要活性成分及其潜在靶点，通过OMIM、TTD、Genecards等数据库获得2型糖尿病相关靶点，运用R3.6.2软件对活性成分靶点和疾病靶点交集，并用Cystoscope 3.7.2软件构建网络图，通过STRING等平台对交集靶点进行蛋白互作、GO功能和KEGG通路富集分析。结果获得没食子酸、没食子单宁、五没食子酰葡萄糖等11个活性成分的83个靶点，进一步与2型糖尿病相关的3015个靶点交集得到核桃成分干预2型糖尿病靶标28个，主要有双氧化酶2、凝血因子2、过氧化氢酶、IL-5和G6PD等。这些靶标涉及激素代谢过程、细胞脂质代谢过程、脂肪酸生物合成过程及胆固醇代谢、对体内体外有机物和无机物的应答反应等GO功能过程，主要参与糖尿病、癌症、循环系统、炎症等四大类17条相关通路及其它内分泌、信号传导、甲状腺和神经递质等相关KEGG通路。结果表明核桃仁可能通过PRKD1、PRKCA、PRKCB、PRKCE、PRKCZ、IL5、F2、CAT、G6PD等多靶点参与MAPK信号通路、AGE-RAGE信号通路、胰岛素抵抗和PI3K-Akt信号通路等信号通路调节脂质代谢，从而实现抗2型糖尿病的作用。

The intervention mechanism of walnut kernel on type 2 diabetes was investigated by meta-analysis in this study. TCMSP database was used to screen the main active ingredients and potential targets of walnut kernels. Targets for type 2 diabetes-related diseases were searched in the OMIM, TTD and genecards databases, and the active component targets and disease targets were intersected using R3.6.2 software. A network diagram was constructed using cystoscope 3.7.2 software. The analyses of protein interaction, GO function and KEGG pathway enrichment were performed on the intersection targets through STRING. As a result, 83 targets of 11 active ingredients, such as gallic acid, gallic tannins and pentagalloylglucose were obtained, which were intersected with 3015 targets related to type 2 diabetes to obtain 28 targets of walnut component for type 2 diabetes intervention, mainly including dioxygenase 2, coagulation factor 2, and catalase, IL5 and glucose-6-phosphate 1-dehydrogenase. These targets involved GO functions such as hormone metabolism, cellular lipid metabolism, fatty acid biosynthesis and cholesterol metabolism, and in vitro and in vivo responses to organic and inorganic substances, which participated mainly in four categories of disorders, diabetes, cancer, circulatory system and inflammation, along with 17related pathways, as well as KEGG pathways such as endocrine, signal transduction, thyroid and neurotransmitter. The results showed that walnut kernels may participate in lipid metabolism regulated by signaling pathways such as MAPK, AGE-RAGE and PI3K-Akt signaling pathways with multiple targets such as PRKD1, PRKCA,PRKCB, PRKCE, PRKCZ, IL5, F2, CAT, and G6PD, to achieve type 2 diabetes intervention effects.

国家自然科学基金项目（81760735）；云南省重大科技专项（生物医药）(2018ZF013；202002AA100005)；云南省科技厅-云南中医学院联合专项重点项目（2019FF002-006）