基于网络药理学痹通汤剂对大鼠脊髓损伤的作用

Effect of Bi-Tong decoction function based on network pharmacology on spinal cord injury in rats

摘要:

[目的] 采用网络药理学与动物实验探讨痹通汤剂对大鼠脊髓损伤（spinal cord injury, SCI）的作用。[方法] 通过TCMSP、Uniprot数据库检索痹通汤剂活性化学成分及靶点；借助GeneCards、CTD、DrugBank数据库获取SCI疾病基因；使用Cytoscape 3.10.0软件构建药物-基因-疾病网络图；借用String数据库进行蛋白互作关系分析；利用David数据库进行GO分析和KEGG通路富集分析。将35只SD大鼠随机分成假手术组、模型组、低剂量组、中剂量组、大剂量组，其中，模型组和各给药组建立SCI模型。记录大鼠BBB（basso-beattie-bresnahan）评分，测量血液学指标。[结果] 筛选出药物靶点350个，药物与疾病交集靶点258个，核心靶点有TNF-α、IL-1β、TP53、ALB、PPARG，核心成分有槲皮素、山奈酚、咖啡酸、木犀草素、芒柄花黄素。21 d，与模型组比较大剂量组BBB评分[分,(13.3±1.0) vs (14.9±0.7), P<0.001]显著增加；28 d，与模型组比较中剂量组[分,(13.7±1.0) vs (15.6±1.0), P<0.001]和大剂量组的BBB评分[分,(13.7±1.0) vs (16.1±1.1), P<0.001]显著增加。血液检测方面，与假手术组比较，模型组、低剂量组、中剂量组、大剂量组中肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）、白介素-1β（interleukin-1β, IL-1β）、IL-6、磷脂酶A2（phospholipase A2, PLA2）、丙二醛（malondialdehyde, MDA）、前列腺素E2（prostaglandin E2, PGE2）均显著升高（P<0.05），超氧化物歧化酶（superoxide dismutase, SOD）显著下降（P<0.05）。与模型组比较，中剂量组、大剂量组TNF-α、IL-1β、PLA2、MDA、PGE2显著下降（P<0.05），大剂量组IL-6显著下降（P<0.05），中剂量组、大剂量组SOD显著上升（P<0.05）。[结论] 痹通汤剂在一定程度上可清除氧自由基，促进脊髓功能恢复。

Abstract:

[Objective] To explore the effect of Bi-Tong decoction on spinal cord injury (SCI) in rats by using network pharmacology and animal experiments. [Methods] The active chemical components and targets of Bi-Tong decoction were retrieved from TCMSP and Uniprot databases. SCI-related genes were obtained from GeneCards, CTD, and DrugBank databases. The drug-gene-disease network was constructed using Cytoscape 3.10.0 software. Protein-protein interaction analysis was performed using the String database. GO analysis, and then KEGG pathway enrichment analysis were conducted using the David database. In addition, thirty-five SD rats were randomly divided into the sham operation group, model group, low-dose group, medium-dose group, and high-dose group. SCI models were established in the model group and each drug administration group. The Basso-Beattie-Bresnahan (BBB) score of rats was recorded, and blood parameters were measured. [Results] In term of network pharmacology, a total of 350 drug targets were screened, with 258 intersection targets between drugs and diseases. Core targets included TNF-α, IL-1β, TP53, ALB, and PPARG, and core components included quercetin, kaempferol, caffeic acid, luteolin, and formononetin. In term of animal experiments, the BBB score in the high-dose group was significantly increased compared with that in the model group at 21 days [points, (13.3±1.0) vs (14.9±0.7), P<0.001], whereas which in the medium-dose group [points, (13.7±1.0) vs (15.6±1.0), P<0.001] and the high-dose group [points, (13.7±1.0) vs (16.1±1.1), P<0.001] were significantly increased compared with that in the model group at 28 days. Regarding blood tests, TNF-α, IL-1β, IL-6, PLA2, MDA, and PGE2 were significantly increased (P<0.05), while SOD was significantly decreased (P<0.05) in the model group, low-dose group, medium-dose group, and high-dose group compared with that in the sham group. Compared with those in the model group, the TNF-α, IL-1β, PLA2, MDA, and PGE2 were significantly decreased in the medium-dose group and high-dose group (P<0.05), whereas the IL-6 was significantly decreased in the high-dose group (P<0.05), and SOD was significantly increased in the medium-dose group and high-dose group (P<0.05). [Conclusion] The Bi-Tong decoction does eliminate oxygen free radicals and promote the recovery of spinal cord function to a certain extent.