目的 研究糖尿病肛瘘创面特异表达LncRNA与mRNA基因功能之间调控网络。方法 用基因芯片技术对糖尿病肛瘘创面和普通肛瘘创面组织中差异性表达的LncRNA及mRNA进行基因表达谱检测，筛选的标准为2倍差异及P < 0.05,再进行差异表达分析，然后对差异表达的mRNAs进行KEGG通路分析及Pathway Map展示，挑选出显著mRNA指标，将这些显著mRNA指标进行q-PCR验证，得到有意义的阳性指标，再将阳性指标与差异LncRNA交集得出LncRNA-mRNA共表达网络，并基于LncRNA-mRNA共表达网络挑选出不同LncRNA进行功能验证。结果 将芯片标准化后分析差异表达的长链非编码RNA和mRNA，发现上调差异有502个，下调差异有1204个；mRNA分析发现上调差异621个，下调差异505个，KEGG通路分析发现上调和下调的通路均有10条；通过分别对上调、下调最明显的通路进行Pathway Map展示，挑选出显著mRNA指标8个：BMP2、IFNB1、IL6、IL18、PIK3CB、SMAD7、SMAD9、β-actin，分别将其进行q-PCR验证，得到有意义的阳性指标个5个：BMP2、IL6、IL18、PIK3CB、SMAD7，将5个阳性指标和差异LncRNA交集得出LncRNA-mRNA共表达网络，并基于LncRNA-mRNA共表达网络挑选出不同LncRNA进行功能验证。结论 挑选出的20个LncRNA（NR_125383、T323486、ENST00000582334、TCONS_00018312、ENST00000418393、TCONS_00017190、TCONS_00019532、ENST00000601559、ENST00000566575、NR_109882、NR_026913、T301537、NR_109774、ENST00000415536、ENST00000610000、ENST00000412485、ENST00000573220、T175957、ENST00000580756、TCONS_00014747）所调控的mRNA居于LncRNA-mRNA共表达网络，其在各个领域当中均有不同程度的报道，为后续的功能和机制研究提供了方向和重点，为加速慢性难愈合和创面愈合的研究提供了新的思路，为开发促愈药物提供基础研究借鉴。

objective to study the regulatory network between specifically expressed LncRNA and mRNA gene function in diabetic anal fistula wounds.Methods Using gene chip technology to detect gene expression profiles of differentially expressed LncRNA and mRNA in diabetic anal fistula wounds and common anal fistula wound tissues, The screening criteria were 2 fold difference and P < 0.05, and then differential expression analysis was performed. Differential expression analysis, Then, KEGG pathway analysis and Pathway Map display were performed on differentially expressed mRNAs. Pick out significant mRNA indicators, These significant mRNA indicators were verified by q-PCR. Get meaningful positive indicators, The positive indicator and the differential LncRNA were then combined to obtain the LncRNA-mRNA co-expression network. Functional verification of different LncRNAs was performed based on the LncRNA-mRNA co-expression network.Results after the chip standardization, 502 up-regulated and 1204 down-regulated long-chain non-coding rnas and mrnas with different expressions were analyzed. MRNA analysis revealed 621 up-regulated pathways and 505 down-regulated pathways, and KEGG pathway analysis revealed 10 up-regulated and down-regulated pathways. Through the Pathway Map display of the most obvious up-regulated and down-regulated pathways, 8 significant mRNA indicators were selected: BMP2, IFNB1, IL6, IL18, PIK3CB, SMAD7, SMAD9, and beta-actin, which were verified by q-pcr, and 5 significant positive indicators were obtained: BMP2, IL6, IL18, PIK3CB and SMAD7 were intersected by the five positive indicators and differentially expressed lncrna-mrna to obtain the lncrna-mrna co-expression network, and different lncrnas were selected based on the lncrna-mrna co-expression network for functional verification.Conclusion the selected 20 lncrna-regulated mrnas are located in the lncrna-mrna co-expression network, and they have reported in various fields to varying degrees, providing direction and focus for the follow-up research on functions and mechanisms, providing new ideas for the research on accelerating the healing of chronic refractory wounds, and providing basic research for the development of healing drugs.

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国家自然科学基金项目（81774325）：基于CNC生物网络图及在体、离体实验差析养阴、回阳机制；负责人：曾娟妮。