摘要：目的：研究木犀草素（Luteolin，Lut）对阿霉素（Doxorubicin，Dox）诱导的人AC16心肌细胞损伤治疗作用转录组学的影响。方法：采用MTT法检测AC16细胞活力，Hoechst33258染色法检测细胞凋亡水平。人AC16心肌细胞设置为正常组、Dox组、Dox加Lut组。正常组加入空白培养基，Dox组加入1μM的Dox，Dox加Lut组加入1μM的Dox及20 μM的Lut。药物作用24 h后，提取各组细胞总RNA，进行转录组测序，并对差异表达基因（DEG）进行基因本体（GO）功能和基因组百科全书（KEGG）通路富集分析。结果：Dox促进了AC16细胞的凋亡（P < 0.05），Lut抑制了Dox诱导的AC16细胞凋亡（P < 0.05）。Dox组与正常组进行比较得到3637个差异基因，其中上调基因1723个，下调基因1914个；Lut加Dox组与Dox组进行比较得到212个差异基因，其中上调基因52个，下调基因160个。选取交集基因，通过GO功能和KEGG富集分析，差异基因主要富集于细胞骨架、细胞囊泡、钙离子内流、内质网应激以及细胞衰老、细胞凋亡等信号通路。结论：木犀草素可通过多靶点抑制阿霉素诱导的人AC16心肌细胞凋亡，其中调控心肌细胞骨架及细胞结构损伤可能是抑制细胞凋亡的关键机制。
Abstract: Objective: To investigate the effect of Luteolin (Lut) on differential expression transcriptome of Doxorubicin (Dox)-induced human AC16 myocardial cell injury model. Methods: Cell viability was tested by MTT assay. Apoptosis was detected by Hoechst33258 staining. Human AC16 myocardial cells were divided into normal group, Dox group, Dox plus Lut group. The normal group was added with medium, Dox group with 1μM Dox, Dox plus Lut group with 1μM Dox plus 20μM Lut. After 24 hours treatment, nucleic acids were extracted from each group for transcriptome sequencing, and genomic ontology (GO) function and KEGG pathway enrichment analysis were performed on differentially expressed genes (DEG). Results: Dox promoted the apoptosis of AC16 cells (P < 0.05), and Lut inhibited dox-induced apoptosis of AC16 cells (P < 0.05). There were 3,637 differentially expressed genes in Dox group and normal group, including 1,723 up-regulated genes and 1,914 down-regulated genes. There were 212 differentially expressed genes in the Lut plus Dox group and Dox group, including 52 up-regulated genes and 160 down-regulated genes. The intersection genes were selected and analyzed by GO function and KEGG enrichment. The differentially expressed genes were mainly enriched in cytoskeleton, cellular vesicles, calcium flow, endoplasmic reticulum stress, senescence, apoptosis and other signaling pathways. Conclusion: Luteolin can inhibit the apoptosis of human AC16 cells induced by dox, the regulation of the structural damage of myocardial cells may be the main mechanism of inhibiting apoptosis.