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贞莲明目胶囊治疗糖尿病视网膜病变的网络药理学机制分析

Analysis of network pharmacological mechanism of Zhenlian Mingmu Capsule in treatment of diabetic retinopathy

    摘要
  • 摘要:
    目的 探讨贞莲明目胶囊治疗糖尿病视网膜病变的作用机制。
    方法 利用网络药理学筛选贞莲明目胶囊治疗糖尿病视网膜病变关键靶点, 并通过分子对接预测活性成分的结合部位。结合网络药理学结果，构建糖尿病视网膜病变大鼠模型。将60只大鼠随机分为正常组、模型组、羟苯磺酸钙片组和贞莲明目胶囊组，每组15只。正常组、模型组给予2 mL生理盐水，每日1次灌胃; 羟苯磺酸钙片组、贞莲明目胶囊组分别给予相应浓度的治疗药物(2 mL), 每日1次灌胃。给药4周后，取大鼠视网膜进行检测，比较视网膜厚度、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)水平和血管内皮生长因子(VEGF)、核转录因子-κB(NF-κB)蛋白表达水平。
    结果 网络药理学共筛选出贞莲明目胶囊有效成分2 367种，作用靶点248个，糖尿病视网膜病变相关靶点3 943个，其交集靶点153个。基因本体(GO)和京都基因与基因组百科全书(KEGG)分析得出主要涉及信号转导、炎症反应、细胞凋亡等生物学反应过程，主要参与IL-1β、EGF/EGFR/P13K/AKT、IL-6/STAT3、肿瘤蛋白P53(TP53)和胱天蛋白酶3(CASP3)等信号通路的调控。分子对接结果表明，筛选得到的主要活性成分与靶点有较强的结合。与正常组比较，模型组大鼠视网膜厚度降低, IL-1β、IL-6、TNF-α、VEGF、NF-κB升高，差异有统计学意义(P < 0.05)。与模型组比较，羟苯磺酸钙片组大鼠视网膜厚度升高, IL-1β、IL-6、TNF-α、VEGF、NF-κB降低，差异有统计学意义(P < 0.05)。与羟苯磺酸钙片组比较，贞莲明目胶囊组大鼠视网膜厚度升高, IL-1β、IL-6、TNF-α、VEGF、NF-κB降低，差异有统计学意义(P < 0.05)。
    结论 贞莲明目胶囊对糖尿病视网膜病变的治疗或许具有积极作用，其作用机制可能与调节IL-1β、EGF/EGFR/P13K/AKT、IL6/STAT3、TP53和CASP3信号通路有关。

     

    Abstract:
    Objective To investigate the mechanism of Zhenlian Mingmu Capsule in the treatment of diabetic retinopathy.
    Methods The key targets of Zhenlian Mingmu Capsule in the treatment of diabetic retinopathy were screened by network pharmacology, and the binding sites of active ingredients were predicted by molecular docking. Combined with the results of network pharmacology, a rat model of diabetic retinopathy was established. Sixty rats were randomly divided into normal group, model group, calcium hydroxybenzene sulfonate tablet group and Zhenlian Mingmu Capsule group, with 15 rats in each group. The normal group and the model group were given 2 mL normal saline and gavage once a day; the calcium hydroxybenzene sulfonate tablet group and Zhenlian Mingmu Capsule group were respectively given the corresponding concentration of therapeutic drugs (2 mL), once a day. After 4 weeks of administration, retinal thickness, interleukin (IL) -1β, IL-6, tumor necrosis factor-α (TNF-α) levels, and protein expression levels of vascular endothelial growth factor (VEGF) and nuclear transcription factor-κB (NF-κB) were measured.
    Results A total of 2 367 active ingredients of Zhenlian Mingmu Capsule were identified by network pharmacology, with 248 targets, 3 943 targets related to diabetic retinopathy, and 153 intersection targets. According to the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), it was mainly involved in biological reaction processes such as signal transduction, inflammation and apoptosis, and mainly involved in the regulation of IL-1β, EGF/EGFR/P13K/AKT, IL-6/STAT3, TP53 and CASP3 signal pathways. The results of molecular docking showed that the main active ingredients obtained by screening had strong binding with the target. Compared with the normal group, retinal thickness in the model group was significantly decreased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly increased (P < 0.05). Compared with the model group, the retinal thickness of rats in the calcium hydroxybenzene sulfonate tablet group was significantly increased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly decreased (P < 0.05). Compared with the calcium hydroxybenzene sulfonate tablet group, retinal thickness in the Zhenlian Mingmu Capsule group was significantly increased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly decreased (P < 0.05).
    Conclusion Zhenlian Mingmu Capsule may have a positive effect in the treatment of diabetic retinopathy, and its mechanism may be related to the regulation of IL-1β, EGF/EGFR/P13K/AKT, IL6/STAT3, TP53 and CASP3 signaling pathways.

     

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