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陆文洪,莫黎,王真权,刘丽芳.网络药理学结合实验验证探究芩柏四物合剂对坏死性筋膜炎术后小鼠炎性反应及高凝状态的影响[J].湖南中医药大学学报,2023,43(3):465-472[点击复制] |
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网络药理学结合实验验证探究芩柏四物合剂对坏死性筋膜炎术后小鼠炎性反应及高凝状态的影响 |
陆文洪,莫黎,王真权,刘丽芳 |
(湖南中医药大学第二附属医院, 湖南 长沙 410005;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
摘要: |
目的 通过网络药理学及实验验证,探究芩柏四物合剂对坏死性筋膜炎(necrotizing fasciitis, NF)术后小鼠模型炎症反应及高凝状态的影响。方法 利用网络药理学方法对芩柏四物合剂-NF相关炎性反应及高凝状态的共同作用靶点进行GO及KEGG富集分析,获取芩柏四物合剂治疗NF的潜在作用机制。将48只小鼠随机分为空白组、芩柏四物合剂组、低分子肝素钠组、模型组。芩柏四物合剂组以芩柏四物合剂水煎液灌胃,空白组和模型组予等体积的生理盐水灌胃,低分子肝素钠组以低分子肝素钠注射液经腹壁皮下注射给药。通过HE染色观察肉芽组织病理形态;利用血细胞分析仪检测全血中的凝血酶原时间(prothrombin time, PT)、D二聚体(D-dimer, D-D)、血小板(platelet, PLT);ELISA检测血清中肿瘤坏死因子-α(tumor necrosis factor-alfa, TNF-α)、白细胞介素-1β(iinterleukin-1 beta, IL-1β)、白细胞介素-6(iinterleukin-6, IL-6)。结果 网络药理学预测发现芩柏四物合剂干预NF主要与IL-17信号通路、TNF信号通路、HIF-1信号通路等联系密切。体内验证试验表明,与空白组相比,在灌胃3、7 d 后,模型组小鼠全血中PT、D-D、PLT升高(P<0.01);与模型组比较,芩柏四物合剂组、低分子肝素钠组小鼠全血中PT、D-D、PLT下降(P<0.01);芩柏四物合剂组与低分子肝素钠组之间无明显差异(P>0.05);芩柏四物合剂组组内比较,PT、D-D、PLT含量在第7 d明显下降,与第3 d比较差异有统计学意义(P<0.05)。此外,与空白组相比,模型组小鼠血清中TNF-α、IL-1β、IL-6水平升高(P<0.01);与模型组比较,芩柏四物合剂组、低分子肝素钠组小鼠血清中TNF-α、IL-1β、IL-6水平下降(P<0.01);芩柏四物合剂组中TNF-α、IL-1β、IL-6水平明显低于低分子肝素钠组(P<0.01);芩柏四物合剂组组内比较,TNF-α、IL-1β、IL-6含量在第7天明显下降,与第3天比较差异有统计学意义(P<0.05)。结论 芩柏四物合剂能通过多成分、多通路改善NF小鼠模型炎症,缓解术后高凝状态,从而有效地改善术后并发症,控制病情。 |
关键词: 芩柏四物合剂 坏死性筋膜炎 炎性反应 高凝状态 网络药理学 中医药 |
DOI:10.3969/j.issn.1674-070X.2023.03.015 |
投稿时间:2022-08-14 |
基金项目:湖南省卫生健康委科研课题(202104010993);湖南中医药大学科研课题一般项目(2020XJJJ057,2020XJJJ060);湖南省普通高等学校教学改革研究项目(HNJG-2021-0586);湖南中医药大学教学改革立项项目(2020-JG042);湖南中医药大学校院联合基金教学改革研究重点项目(2022-LHJG003)。 |
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Effects of Qinbai Siwu Mixture on inflammatory response and hypercoagulability of necrotizing fasciitis mice after operation based on network pharmacology and experimental veirification |
LU Wenhong,MO Li,WANG Zhenquan,LIU Lifang |
(The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
Abstract: |
Objective To investigate the effects of Qingbai Siwu Mixture (QBSWM) on inflammatory response and hypercoagulability of mice after necrotizing fasciitis (NF) operation by establishing mice model after NF operation. Methods GO and KEGG enrichment analysis were carried out for QBSWM-NF related inflammatory response and hypercoagulable state by network pharmacology to identiry the potential mechanism of QBSWM in treating NF. Forty-eight mice were randomized into blank group, QBSWM group, low molecular weight heparinsodium (LMWHS) group and model group. QBSWM group was given the decoction of QBSWM intragastrically, blank group and model group were given the same volume of normal saline, LMWHS group received subcutaneous injection of LMWHS through abdominal wall. HE staining was used to observe the morphology of granulation tissue, prothrombin time (PT), D-dimer (D-D) and platelets (PLT) in whole blood were detected by hematology analyzer, and serum tumor necrosis factor-alfa (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were detected by ELISA to evaluate the effects of QBSWM on inflammatory response and hypercoagulability in mouse after NF operation. Results Model group had significantly higher content of PT, D-D and PLT than blank group at 3, 7 d after intragastric administration (P<0.01); while QBSWM group and LMWHS group showed significantly lower content of PT, D-D and PLT than model group (P<0.01); no significant difference was found between QBSWM group and LMWHS group (P>0.05) for the content of PT, D-D and PLT. In addition, compared with blank group, the content of TNF-α, IL-1β and IL-6 in serum of model group significantly increased (P<0.01); compared with model group, the content of TNF-α, IL-1β and IL-6 in serum of QBSWM group and LMWHS group significantly decreased (P<0.01); the content of TNF-α, IL-1β and IL-6 in the QBSWM group were significantly lower than those in LMWHS group (P<0.01). Conclusion QBSWM can significantly reduce the inflammatory indicators of mice after NF operation, alleviate inflammatory response, relieve the postoperative hypercoagulability state, thus effectively improve the postoperative complications and control the disease. |
Key words: Qinbai Siwu Mixture necrotizing fasciitis inflammatory reaction hypercoagulability network pharmacology Chinese medicine |
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