目的:神经性疼痛(NP)在普通人群中发病率高,与焦虑症密切相关,并对生活质量产生负面影响。大麻二酚(CBD),作为一种天然产品,已广泛研究了其对疼痛和抑郁(DP)等症状的潜在治疗作用。然而,CBD改善NP伴抑郁症的机制尚不完全清楚。
方法:首先,我们使用生物信息学工具来深入挖掘与NP相关的交叉基因,DP,和CBD。其次,通过蛋白质-蛋白质相互作用网络筛选核心靶标,基因本体论,京都基因和基因组分析百科全书,分子对接和分子动力学模拟。接下来,使用行为测试评估CBD干预对脊神经结扎(SNL)小鼠模型中疼痛和抑郁行为的影响,并绘制剂量反应曲线。在确定最佳干预剂量后,通过Westernblot(WB)和定量聚合酶链反应(qPCR)验证核心靶标.最后,我们通过Nissl染色研究了CBD的潜在机制,免疫荧光(IF)和透射电子显微镜(TEM)。
结果:通过生物信息学分析筛选出与NP和DP最相关的5个CBD核心基因,包括PTGS2、GPR55、SOD1、CYP1A2和NQO1。行为测试结果表明,CBD经腹腔给药5mg/kg可明显改善SNL小鼠的疼痛行为和抑郁状态。WB,qPCR,如果,TEM实验进一步证实了CBD对关键分子的调节作用。
结论:在这项研究中,我们在DP治疗NP中发现了CBD的五个靶点。这些发现为CBD作为潜在的治疗剂提供了进一步的理论和实验基础。
OBJECTIVE: Neuropathic pain (NP) has a high incidence in the general population, is closely related to anxiety disorders, and has a negative impact on the quality of life. Cannabidiol (CBD), as a natural product, has been extensively studied for its potential therapeutic effects on symptoms such as pain and depression (DP). However, the mechanism of CBD in improving NP with depression is not fully understood.
METHODS: First, we used bioinformatics tools to deeply mine the intersection genes associated with NP, DP, and CBD. Secondly, the core targets were screened by Protein-protein interaction network, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, molecular docking and molecular dynamics simulation. Next, the effects of CBD intervention on pain and depressive behaviors in the spinal nerve ligation (SNL) mouse model were evaluated using behavioral tests, and dose-response curves were plotted. After the optimal intervention dose was determined, the core targets were verified by Western blot (WB) and Quantitative Polymerase Chain Reaction (qPCR). Finally, we investigated the potential mechanism of CBD by Nissl staining, Immunofluorescence (IF) and Transmission Electron Microscopy (TEM).
RESULTS: A total of five core genes of CBD most associated with NP and DP were screened by bioinformatics analysis, including PTGS2, GPR55, SOD1, CYP1A2 and NQO1. Behavioral test results showed that CBD by intraperitoneal administration 5mg/kg can significantly improve the pain behavior and depressive state of SNL mice. WB, qPCR, IF, and TEM experiments further confirmed the regulatory effects of CBD on key molecules.
CONCLUSIONS: In this study, we found five targets of CBD in the treatment of NP with DP. These findings provide further theoretical and experimental basis for CBD as a potential therapeutic agent.