| 基于GEO数据库和网络药理学探讨柴胡-葛根治疗原发性青光眼的机制 |
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| 引用本文： | 杨稀瑞,王继雪,袁星星,董霏雪,赵辉.基于GEO数据库和网络药理学探讨柴胡-葛根治疗原发性青光眼的机制[J].眼科新进展,2022,0(8):603-607. |
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| 作者姓名： | 杨稀瑞 王继雪 袁星星 董霏雪 赵辉 |
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| 作者单位： | 450000 河南省郑州市，河南中医药大学第一附属医院眼科（杨稀瑞，王继雪，赵辉）；150001 黑龙江省哈尔滨市，中医药科学院南岗分院（袁星星）；150040 黑龙江省哈尔滨市，黑龙江中医药大学附属第一医院（董霏雪） |
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| 摘 要： | 目的 基于GEO数据库和网络药理学探讨柴胡-葛根治疗原发性青光眼的机制，为原发性青光眼的治疗提供新方向。方法 通过TCMSP数据库筛选柴胡、葛根的有效活性成分；通过检索GeneCards、OMIM等数据库及二次挖掘GEO数据库中的芯片数据筛选原发性青光眼的作用靶点；利用David平台对靶基因进行GO功能及KEGG富集分析。体外实验以小鼠视网膜神经节细胞（RGC）为研究对象，以过氧化氢诱导RGC构建氧化应激损伤模型，设置空白组、模型组、空白+中药组、模型+中药组，倒置相差显微镜下观察各组RGC形态变化，RT-PCR检测各组RGC中PI3K和AKT mRNA表达情况。结果 网络药理学研究结果证实，与原发性青光眼相关的差异蛋白靶点共63个，包括IL-6、VEGFA等。GO功能及KEGG富集分析结果显示，柴胡-葛根治疗原发性青光眼的生物学过程与蛋白结合、催化、有机环状化合物结合及有机物代谢过程等有关，主要通过调节PI3K-AKT、TNF、MAPK、VEGF、JAK-STAT等信号通路发挥作用。体外实验结果显示，模型+中药组RGC从缓慢贴壁到完全贴壁，并可见少量聚集性生长及串珠样排列，细胞体缓慢增大。RT-PCR检测结果显示，与空白组相比，空白+中药组RGC中PI3K和AKT mRNA表达均下降（均为P<0.05）；与模型组相比，模型+中药组RGC中PI3K和AKT mRNA表达均下降（均为P<0.05）。结论 柴胡-葛根能够通过抑制PI3K-AKT信号通路抑制细胞凋亡，起到改善原发性青光眼的作用。
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| 关 键 词： | GEO数据库 网络药理学 柴胡-葛根 原发性青光眼 视网膜神经节细胞 |
Mechanism of radix bupleuri and puerariae in the treatment of primary glaucoma based on GEO database and network pharmacology |
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| YANG Xirui,WANG Jixue,YUAN Xingxing,DONG Feixue,ZHAO Hui.Mechanism of radix bupleuri and puerariae in the treatment of primary glaucoma based on GEO database and network pharmacology[J].Recent Advances in Ophthalmology,2022,0(8):603-607. |
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| Authors: | YANG Xirui WANG Jixue YUAN Xingxing DONG Feixue ZHAO Hui |
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| Affiliation: | 1.Department of Ophthalmology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,Henan Province,China2.Nangang Branch of Heilongjiang College of Traditional Chinese Medicine,Harbin 150001,Heilongjiang Province, China3.The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,Heilongjiang Province,China |
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| Abstract: | Objective To explore the mechanism of radix bupleuri and puerariae in the treatment of primary glaucoma based on network pharmacology combined with the GEO database, thus providing a new direction for the treatment of primary glaucoma. Methods The active constituents of radix bupleuri and puerariae were screened from the TCMSP database. The targets of primary glaucoma were screened from GeneCards, OMIM, and chip data in the GEO database. David platform was used for GO function and KEGG enrichment analysis of target genes. In vitro experiments, retinal ganglion cells (RGCs) in mice were induced by hydrogen peroxide to build oxidative stress injury models. They were divided into the blank group, model group, blank+TCM group, and model+TCM group. The morphological changes of RGCs in each group were observed under an inverted phase contrast microscope. The mRNA levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) were detected by real-time polymerase chain reaction (RT-PCR). Results The network pharmacology-based results confirmed that there were 63 differential protein targets related to primary glaucoma, including interleukin 6 and vascular endothelial growth factor A (VEGF-A). GO function and KEGG enrichment analysis results showed that the biological process of treating primary glaucoma with radix bupleuri and puerariae was related to protein binding, catalysis, organic cyclic compound binding, and organic metabolism, and that radix bupleuri and puerariae played a role in the treatment of primary glaucoma by regulating PI3K-AKT, TNF, MAPK, VEGF, and JAK-STAT signal pathways. The in vitro experimental results showed that RGCs in the model+TCM group slowly and fully adhered to the wall, some grew in a cluster or in a string of beads, and cell bodies enlarged slowly. RT-PCR results showed that compared with the blank group, the mRNA levels of PI3K and AKT in the blank+TCM group decreased (both P<0.05), and that compared with the model group, the mRNA levels of PI3K and AKT in the model+TCM group decreased (both P<0.05). Conclusion Radix bupleuri and puerariae can improve primary glaucoma by inhibiting the PI3K/AKT signal pathway and apoptosis. |
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| Keywords: | GEO database network pharmacology radix bupleuri and puerariae primary glaucoma retinal ganglion cells |
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