基于抑郁模型大鼠miR-665表达及靶基因功能分析探讨开心解郁方抗抑郁疗效机制

摘 要：目的：检测中药开心解郁方干预抑郁症模型大鼠过程中海马miR-665表达变化并对miR-665的靶基因进行生物信息分析，探讨miR-665在抑郁症的发病及开心解郁方抗抑郁机制中的作用。方法：建立慢性应激抑郁症大鼠模型并用开心解郁方干预42天，取海马组织提取总RNA，采用RT-qPCR检测各组大鼠海马miR-665相对表达量，采用TargetScan和microRNAorg数据库对miR-665进行靶基因预测，采用DAVID数据库对预测得到的靶基因进行GO功能富集分类及KEGG信号通路分析。结果：与正常组比较，模型组大鼠海马miR-665表达水平显著增高，差异具有统计学意义（P<0.01）；与模型组比较，中药组及西药组大鼠海马miR-665表达水平显著降低，差异具有统计学意义（P<0.05）。miR-665靶基因的生物学功能主要富集于有机物质反应等；信号通路主要富集于N-糖链的合成等。结论：miR-665可能参与了抑郁症病理机制过程调控，通过改善其表达异常可能为开心解郁方的抗抑郁机制之一，通过对其靶基因的功能预测分析对于后期继续研究开心解郁方干预miR-665的具体作用机制提供了方向和理论基础。

Expression of miR-665 And Bioinformatic Analysis on Its Target Genes of Kai-Xin Jie-Yu Decoction Based on Depression Model Rats

Abstract: This study was aimed to detect the expression of miR-665 in the hippocampal of depression rat model treated with Kai-Xin Jie-Yu (KXJY) decoction and bioinformatic analysis of target genes of miR-665, in order to investigate the role of miR-665 in the pathogenesis of depression and the antidepressant mechanism of KXJY decoction. The rat model of chronic stress depression was established and then treated with KXJY decoction for 42 days. The total RNA from hippocampus tissues was extracted. And the relative expression of miR-665 in hippocampus of rats in each group was detected by RT-qPCR. TargetScan and microRNAorg databases were used to predict target genes for miR-665. DAVID database was used to classify GO function and to analyze KEGG signaling pathway of target genes. The results showed that compared with the normal group, the expression level of miR-665 in hippocampus of the model group was significantly higher with significant difference (P < 0.01). Compared with the model group, the expression level of miR-665 in hippocampus of Chinese medicine group and western medicine group decreased significantly with significant difference (P < 0.01). The biological functions of miR-665 target genes were mainly concentrated in the response to organic substance. The signal pathway was mainly concentrated in N-Glycan biosynthesis. It was concluded that miR-665 may be involved in the pathological process of depression, by correcting the abnormal expression of miR-665, which may be one of the antidepressant mechanisms of KXJY decoction. Through the analysis and prediction of the target genes, it provided a certain direction and theoretical basis for further study on the specific mechanism of KXJY decoction intervention on miR-665.