The Toll-like receptor 4 antagonist TAK-242 in combination with sodium hyaluronate alleviates postoperative abdominal adhesion in a mouse model.

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-10-25 DOI:10.1186/s12920-024-02031-1
Dong Liu, Haochongyang Tong, Yu Guo, Bin Liu, Changchun Ye, Ni Yang, Yunhua Wu
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Abstract

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. The Toll-like receptor 4 (TLR4) signaling pathway is one of the most common inflammation-related pathways, and it has been demonstrated that TLR4 is highly expressed in adhesive tissues; however, the function of TLR4 in adhesion formation has not yet been studied. In the present study, the expression of TLR4 was first detected by immunohistochemical (IHC) and double-immunofluorescence staining in 40 mice, which were randomly divided into four groups, and sacrificed at 1, 3, 5 and 7 days after surgery. Subsequently, another 40 mice were randomly divided into five groups; with the exception of the sham group, the other groups were modeled and treated with saline that contained DMSO, sodium hyaluronate (HA), TAK-242 or TAK-242 + HA (applied to damaged peritoneal wounds). A total of 7 days after surgery, the mice were sacrificed and specimens were collected. Inflammation was detected by hematoxylin and eosin staining, and ELISA of transforming growth factor- β1 (TGF-β1) and interleukin-6 (IL-6); collagen deposition was examined by Masson staining and IHC staining of α-SMA; and reactive oxygen species (ROS) were detected by ROS staining and malondialdehyde (MDA) assay. The results revealed that TLR4 was highly expressed in the adhesive tissues at 3, 5 and 7 days after surgery. In addition, TAK-242 + HA treatment could reduce abdominal adhesion formation, exhibiting lower Nair's score and inflammation scores, lower TGF-β1 and IL-6 levels, and lower collagen thickness and α-SMA levels compared with those in the control group. In addition, the TAK-242 + HA group had lower levels of ROS and MDA compared with those in the control group. The present study revealed that TLR4 was highly expressed in the process of adhesion formation and its inhibitor, TAK-242, combined with HA, could reduce adhesion formation by reducing inflammation and ROS, and alleviating collagen deposition.

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Toll样受体4拮抗剂TAK-242与透明质酸钠联合使用可减轻小鼠模型的术后腹腔粘连。
术后腹腔粘连是腹部手术后最常见的并发症之一。Toll 样受体 4(TLR4)信号通路是最常见的炎症相关通路之一,已有研究证明 TLR4 在粘连组织中高表达,但 TLR4 在粘连形成中的功能尚未得到研究。在本研究中,首先通过免疫组化(IHC)和双免疫荧光染色检测了 40 只小鼠的 TLR4 表达,将小鼠随机分为四组,分别于术后 1、3、5 和 7 天处死。随后,将另外 40 只小鼠随机分为五组;除假组外,其他各组均进行模型制作,并用含有二甲基亚砜的生理盐水、透明质酸钠(HA)、TAK-242 或 TAK-242 + HA(涂抹在受损的腹膜伤口上)进行处理。手术共 7 天后,小鼠被处死并收集标本。通过苏木精和伊红染色、转化生长因子-β1(TGF-β1)和白细胞介素-6(IL-6)ELISA检测炎症;通过Masson染色和α-SMA IHC染色检测胶原沉积;通过ROS染色和丙二醛(MDA)检测活性氧(ROS)。结果显示,术后3天、5天和7天,TLR4在粘连组织中高表达。此外,与对照组相比,TAK-242 + HA 治疗可减少腹腔粘连的形成,Nair 评分和炎症评分降低,TGF-β1 和 IL-6 水平降低,胶原厚度和 α-SMA 水平降低。此外,与对照组相比,TAK-242 + HA 组的 ROS 和 MDA 水平较低。本研究揭示了 TLR4 在粘连形成过程中的高表达,其抑制剂 TAK-242 与 HA 联用可通过减少炎症和 ROS,减轻胶原沉积,从而减少粘连的形成。
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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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