Anti-fibrotic Therapies for Prevention of Abdominal Adhesion

Background. Postoperative abdominal adhesion remains one of the frequent complications after abdominal surgery and lacks effective intervention. Peritoneal mesothelial cell injury and healing play crucial roles in the process of adhesion formation, and identifying this mechanism might provide new insight into possible new therapeutic strategies for this disease. Transmembrane and immunoglobulin domain-containing 1 (TMIGD1) has been proven to protect renal epithelial cells from injury induced by oxidative stress and has also been identified as a novel adhesion molecule. Here, we investigated the role of TMIGD1 and its possible mechanism in adhesion formation. Materials and Methods. Immunohistochemistry (IHC), qPCR, and immunofluorescence (IHF) were used to detect the expression of TMIGD1. The grade and tenacity score of adhesion were used to evaluate the adhesion formation conditions. A TMIGD1-overexpressing HMrSV5 cell line was established. MTT assay, Western blotting, Annexin V apoptosis analysis, and CK19 staining were used to measure mesothelial cell viability, apoptosis, and completeness. ROS and MDA detection were used to measure mesothelial cell oxidative stress levels. JC-1 staining, IHF, and transmission electron microscopy were performed to assess mitochondrial function. Scratch-wound and adhesion assays were used to evaluate the adhesion ability of mesothelial cells. Results. First, we showed that TMIGD1 was decreased in mouse abdominal adhesion tissue and peritoneal mesothelial cells. Second, TMIGD1 overexpression inhibited adhesion formation. Third, TMIGD1 overexpression protected mesothelial cells from hydrogen peroxide- (H2O2-) induced oxidative stress injury. Fourth, TMIGD1 overexpression alleviated oxidative stress by protecting the mitochondrial function of mesothelial cells. In addition, TMIGD1 overexpression enhanced mesothelial cell adhesion. Conclusion. Our findings suggest that TMIGD1 protects mesothelial cells from oxidative stress injury by protecting their mitochondrial function, which is decreased in regular abdominal adhesion tissue. In addition, TMIGD1 enhances peritoneal mesothelial cell adhesion to promote healing.

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P044 ATRAUMATIC AND CONSISTENT HERNIA MESH FIXATION: PERFORMANCE AND SAFETY IN A LAPAROSCOPIC IPOM PORCINE MODEL

British Journal of Surgery ◽

10.1093/bjs/znab395.040 ◽

2021 ◽

Vol 108 (Supplement_8) ◽

Author(s):

Miguel Lopes ◽

Elisa Bitton ◽

Elise Devries ◽

Maria Pereira

Keyword(s):

Histological Analysis ◽

Porcine Model ◽

Mesh Fixation ◽

Fixation Strength ◽

Tissue Ingrowth ◽

Hernia Mesh ◽

Local Tissue ◽

Abdominal Adhesion ◽

Mesh Shrinkage

Abstract Aim Demonstrate the performance and safety of TISSIUM on-demand activated adhesive for atraumatic hernia mesh fixation in a laparoscopic IPOM porcine model. Material and Methods Full thickness 4 cm in diameter excisional abdominal defects (n = 14) were created in pig (n = 8). The defects were repaired through laparoscopic intraperitoneal mesh placement using commercial composite meshes fixed with TISSIUM adhesive (n = 8) or resorbable tacks (n = 6). The animals were sacrificed after 28 and 90 days. An independent pathologist evaluated abdominal adhesion, mesh shrinkage, local tissue tolerance and tissue ingrowth through histological analysis (H&E and Movat Pentacrome) at sacrifice. Fixation strength of the explanted abdominal walls was also assessed via burst-ball. Results No adverse events were observed at implantation or during the survival period. All the meshes were in place at sacrifice. Mesh shrinkage and abdominal adhesion scores were similar between the two groups. Histological analysis of the mesh demonstrated equivalent quality of tissue ingrowth and excellent local tissue tolerance with minimal/mild foreign body response and mononuclear cells inflammation. The repair strength, evaluated through a burst ball method 90 days after implantation, showed no significant difference between the TISSIUM adhesive and tacks. Usability is currently being evaluated in clinically relevant models. Conclusions In this preclinical study the TISSIUM adhesive demonstrated similar fixation strength and quality of repair when compared to commercial tacks. This technology has the potential to impact hernia procedures standardization and reduce pain often associated with current fixation technologies.

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Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/4591384 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Yunhua Wu ◽

Guangbing Wei ◽

Junhui Yu ◽

Zilu Chen ◽

Zhengshui Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Model ◽

Transforming Growth Factor ◽

High Dose ◽

Collagen Deposition ◽

Abdominal Adhesions ◽

Abdominal Adhesion ◽

Danhong Injection ◽

Intestinal Adhesion ◽

And Oxidative Stress

Background. Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model. Materials and Methods. Forty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair’s scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress. Results. The intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-β1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs. Conclusion. DHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

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