Ke-Qian Liu, Xue Bai, Ji-Lin Chen, Guo-Jiao Chen, Muhammad Ameen Jamal, Yu-Qi He
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The cross-targets of SX granules and ICH were obtained using network pharmacology, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed. Then, the obtained Hub genes were verified using real-time quantitative polymerase chain reaction (RT-qPCR). The mNSS score was reduced and the duration to remain wire suspended increased in the SX group. In the morphological experiment, SX granules reduced brain tissue damage, neuronal apoptosis, and the number of astrocytes in the ICH rats. Moreover, 607 targets of drug–disease intersection were obtained by network pharmacology, and 10 Hub genes were found. SX granules regulated the expression of HRAS, MAPK3, and STAT3 in ICH condition. 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引用次数: 0
摘要
我们的目的是在实验和网络药理学的基础上,探讨歙县化瘀活血颗粒(SX颗粒)治疗脑出血(ICH)的药理作用和分子网络机制。建立 ICH 模型后,通过改良神经严重程度评分(mNSS)、悬丝试验和转体试验评估大鼠的行为功能。使用2,3,5-三苯基氯化四氮唑(TTC)、苏木精-伊红(HE)、Nissl和TdT介导的dUTP缺口末端标记(TUNEL)结合神经元核(NEUN)免疫荧光染色观察脑组织形态学变化。通过网络药理学、基因本体(GO)富集分析和京都基因组百科全书(KEGG)信号通路分析,获得了SX颗粒和ICH的交叉靶标。然后,利用实时定量聚合酶链反应(RT-qPCR)对获得的 Hub 基因进行验证。在 SX 组中,mNSS 评分降低,保持钢丝悬浮的时间延长。在形态学实验中,SX 颗粒减少了 ICH 大鼠的脑组织损伤、神经元凋亡和星形胶质细胞数量。此外,通过网络药理学还获得了607个药物-疾病交叉靶点,并发现了10个Hub基因。SX颗粒能调节ICH状态下HRAS、MAPK3和STAT3的表达。总之,SX颗粒能改善ICH大鼠的行为功能障碍、脑组织异常改变和细胞形态,其潜在的分子机制与多个基因的表达有关。
Molecular network mechanism of Shexiang Huayu Xingnao granules in treating intracerebral hemorrhage
We aim to explore the pharmacological efficacy and molecular network mechanism of Shexiang Huayu Xingnao granules (SX granules) in the treatment of intracerebral hemorrhage (ICH) based on experiments and network pharmacology. After the ICH model establishment, the behavioral functions of rats were assessed by the modified neurological severity score (mNSS), the wire suspension test, and the rotarod test. Brain histomorphological changes were observed using 2,3,5-triphenyl tetrazolium chloride (TTC), hematoxylin–eosin (HE), Nissl, and TdT-mediated dUTP nick end labeling (TUNEL) combined with neuronal nuclear (NEUN) immunofluorescence staining. The cross-targets of SX granules and ICH were obtained using network pharmacology, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed. Then, the obtained Hub genes were verified using real-time quantitative polymerase chain reaction (RT-qPCR). The mNSS score was reduced and the duration to remain wire suspended increased in the SX group. In the morphological experiment, SX granules reduced brain tissue damage, neuronal apoptosis, and the number of astrocytes in the ICH rats. Moreover, 607 targets of drug–disease intersection were obtained by network pharmacology, and 10 Hub genes were found. SX granules regulated the expression of HRAS, MAPK3, and STAT3 in ICH condition. In conclusion, SX granules improved behavioral dysfunction, abnormal alterations in brain tissue, and cell morphology in ICH rats, and potential molecular mechanism was linked with the expression of multiple genes.