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目的:探讨大电导钙激活钾通道(BKCa)基因敲除后大鼠胰腺转录组基因表达及信号转导通路变化，分析BKCa基因在胰腺中的作用。方法:3只BKCa基因敲除成年雌性SD大鼠(BKCa敲除组)由首都医科大学基础医学院生理学与病理生理学系王伟教授馈赠，设3只野生型成年雌性SD大鼠为野生组。取完整的胰腺组织，提取总RNA，采用转录组测序技术进行测序、差异分析软件DESeq2筛选BKCa敲除组和野生组胰腺组织间的差异表达基因，利用基因本体(GO)和京都基因与基因组百科全书(KEGG)数据库对差异表达基因进行生物功能富集分析。采用RT-PCR法对富集分析出的关键基因进行验证。结果:BKCa敲除组和野生组大鼠胰腺样本共检测到18 258个基因，经DESeq2软件筛选出348个表达差异基因，其中200个基因在BKCa敲除组胰腺中高表达，148个基因低表达。GO数据库显示214个差异表达基因富集在56个GO条目，其中24个涉及生物学过程，18个涉及细胞组分，14个涉及分子功能；KEGG数据库显示348个差异表达基因中15个富集于PI3K/Akt信号通路，经RT-PCR验证，其关键基因Hsp90ab1、Hsp90aa1、Foxo3a、Col1a2在BKCa敲除组胰腺组织的表达显著高于野生组(n P<0.0001)，而Thbs1、Pik3r1和Ppp基因表达差异无统计学意义。n 结论:在转录组水平上筛选出BKCa敲除组与野生组大鼠差异表达基因，其显著富集于PI3K/Akt信号通路，为预测BKCa在胰腺中发挥的功能提供了线索。“,”Objective:To investigate the differences of gene expression and signal transduction pathways in large conductance calcium-activated potassium channels(BKCa) gene knockout rats and analyze the role of BKCa gene in pancreas.Methods:Three adult female BKCa knockout SD rats (BKCa knockout group) were donated by Professor Wang Wei from Department of Pathology and Physiology of Basic Medical College of Capital Medical University, and three wild type adult femal SD rats were used as wide-type group. The whole pancreas was resected and RNA was extracted. RNA transcriptome sequencing (RNA-seq) technology was used for sequencing and DESeq2 differentiation analysis software was used for screening differentially expressed genes between two groups, and the gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed. The key genes were validated by RT-PCR.Results:18 258 genes were detected by sequencing in the 2 groups. There were statistically significant differences in the expression of 348 genes screened by DESeq2, 200 of which were highly expressed in the pancreas of BKCa knockout group, and 148 of which were low-expressed. 214 differentially expressed genes enrichments were found in GO database, including 25 involved in biological process, 18 in cell components and 14 molecular functions. All 348 differentially expressed genes were found in KEGG database, 15 of which were significantly enriched in PI3K/Akt signaling pathways. RT-PCR results showed that the expression of key genes Hsp90ab1, Hsp90aa1, Foxo3a and Col1a2 in the BKCa knockout group was significantly higher than that in wide type group (n P<0.0001), while Thbs1, Pik3r1 and Ppp genes were not significantly different.n Conclusions:Differentially expressed genes and related important regulatory signaling pathways were screened out between BKCa knockout SD rats and wild-type SD rats at the transcriptional level, and PI3K/Akt pathway was found to be the most enriched, providing an important clue for predicting the function of BKCa in the pancreas.