基于GEO数据库的脑卒中相关靶点挖掘及与瓜子金皂苷己分子对接研究

Mining of stroke-related targets based on GEO database and docking with Polygalasaponin F

目的:基于GEO数据库挖掘脑缺血再灌注损伤(Cerebral ischemia-reperfusion injury,CIRI)中的关键靶点,并通过分子对接探讨瓜子金皂苷己(Polygalasaponin F,PGSF)抗CIRI的作用机制。方法:选择GEO数据库中CIRI芯片,应用R语言分析芯片的矩阵文件,筛选表达差异靶点,对结果进行可视化处理;将差异显著的靶点进行蛋白-蛋白相互作用分析,构建网络并根据拓扑参数筛选关键靶点。采用AutoDock Tools软件对PGSF与上述关键靶点进行分子对接,计算结合能。结果:通过GEO数据库筛选出CIRI差异表达靶点137个,在蛋白-蛋白相互作用网络中筛选得到关键靶点为:白细胞介素6(Interleukin-6,IL-6)、基质金属蛋白酶9(Matrix Metallopeptidase 9,MMP9)、CC型趋化因子配体2(C-C motif chemokine 2,CCL2)、细胞间黏附分子1(Intercellular adhesion molecule,ICAM1)和前列腺素G/H合酶2(Prostaglandin G/H synthase 2,PTGS2),PGSF与关键靶点对接得分为:-8.8、-7.3、-8.9、-7.9、-9.4 Kj/mol,说明PGSF可能与关键靶点结合,且具有较强的亲和力。结论:PGSF抗CIRI的作用机制可能与调控IL-6、MMP9、CCL2、ICAM1和PTGS2发挥抗炎、抑制血脑屏障破坏和减轻脑水肿有关。

Objective:To explore the key targets in cerebral ischemia-reperfusion injury(CIRI)based on GEO database,and to explore the mechanism of Polygalasaponin F(PGSF)against CIRI through molecular docking.Methods:The CIRI chip was selected in GEO database,using R language to analyze the matrix file of the chip,screening differentially expressed targets,and visualizing the results.Protein-protein interaction analysis was performed on the targets with significant differences,and the network was constructed and the key targets were screened according to the topological parameters.Molecular docking of PGSF with the above key targets was performed using AutoDock Tools software to calculate the binding energy.Results:Totally 137 differentially expressed targets in CIRI were screened through the GEO database,the key targets screened in the protein-protein interaction network were:Interleukin-6(IL-6)and Matrix Metallopeptidase 9(MMP9),CC motif chemokine 2(CCL2),Intercellular adhesion molecule 1(ICAM1)and Prostaglandin G/H synthase 2(PTGS2),and the scores for the docking of PGSF with the key targets were:-8.8Kj/mol,-7.3 Kj/mol,-8.9 Kj/mol,-7.9 Kj/mol,-9.4 Kj/mol,indicating that PGSF might be bind with the key targets,and it showed potent affinity.Conclusion:The anti-CIRI mechanism of PGSF may be related to the regulation of IL-6,MMP9,CCL2,ICAM1 and PTGS2 to exert anti-inflammatory,inhibit the disruption of the blood-brain barrier and reduce cerebral edema.