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[洗剂通过下调炎性因子和抑制炎症促进肛瘘大鼠模型的术后伤口愈合]

[ Lotion promotes postoperative wound healing in a rat model of anal fistula by downregulating inflammatory factors and suppressing inflammation].

作者信息

Wang L, Qi W, Gao J, Tian M, Xu J

机构信息

Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, China.

School Hospital, Hebei Normal University, Shijiazhuang 050010, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2024 Jul 20;44(7):1256-1265. doi: 10.12122/j.issn.1673-4254.2024.07.05.

Abstract

OBJECTIVE

To explore the mechanism of Lotion (TYX) for promoting wound healing following surgery for anal fistula.

METHODS

The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases, and the targets associated with wound healing were screened using GeneCards and OMIM databases; the intersecting drug and wound-related targets were analyzed with protein-protein interaction (PPI) analysis and GO and KEGG enrichment analyses. In 25 SD rat models with simulated anal fistula surgery, the effect of wound dressing with TYX at low, medium and high doses (once daily for 14 days) on wound healing were assessed in comparison with potassium permanganate (PP) solution. The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF- expression using immunohistochemistry. The expressions of 1β, TNF-, IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR, Western blotting or ELISA.

RESULTS

Network pharmacology analysis yielded 156 common targets between TYX and wound healing, and among them IL-1β, TNF- , and IL-6 were identified as potential targets of TYX for promoting wound healing. Six core components of TYX were capable of binding to IL-1β, TNF-, and IL-6 with binding energies all below -6.0 Kcal/mol. In the rat models, the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition. TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6, IL-1β, TNF- mRNA and IL-6 protein in the granulation tissues, but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF- protein expression and mRNA expressions of TNF- and IL-6.

CONCLUSION

TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

摘要

目的

探讨痛疡消洗剂(TYX)促进肛瘘术后创面愈合的机制。

方法

利用中药系统药理学数据库与分析平台(TCMSP)和中药分子机制生物信息学分析工具(BATMAN)数据库探究TYX的活性成分和药物靶点,使用基因卡片(GeneCards)和在线孟德尔人类遗传数据库(OMIM)筛选与创面愈合相关的靶点;通过蛋白质-蛋白质相互作用(PPI)分析以及基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析对药物与创面相关的交集靶点进行分析。将25只模拟肛瘘手术的SD大鼠模型分为3组,分别用低、中、高剂量TYX(每日1次,共14天)和高锰酸钾(PP)溶液进行创面换药,比较其对创面愈合的影响。取创面肉芽组织进行苏木精-伊红(HE)染色观察病理变化,采用免疫组织化学法检测肿瘤坏死因子(TNF-)表达。运用实时荧光定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法(Western blotting)或酶联免疫吸附测定(ELISA)检测肉芽组织中白细胞介素1β(IL-1β)、TNF-、白细胞介素6(IL-6)mRNA及蛋白表达。

结果

网络药理学分析得出TYX与创面愈合的156个共同靶点,其中IL-1β、TNF-、IL-6被确定为TYX促进创面愈合的潜在靶点。TYX的6种核心成分能够与IL-1β、TNF-、IL-6结合,结合能均低于-6.0千卡/摩尔。在大鼠模型中,TYX组和PP溶液组创面换药后炎症细胞浸润明显减少,成纤维细胞及胶原沉积增加。3种剂量TYX组和PP溶液组均能显著降低肉芽组织中IL-6、IL-1β、TNF-mRNA及IL-6蛋白表达,但中、高剂量TYX组在降低TNF-蛋白表达及TNF-、IL-6 mRNA表达方面作用明显强于PP溶液组。

结论

TYX通过下调炎症因子表达、减轻创面炎症反应来加速创面愈合。

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