The Toll-like receptor 4 antagonist TAK-242 alleviates postoperative abdominal adhesion in a mouse model

Abstract

Abstract Background Postoperative abdominal adhesion is a common complication after abdominal surgery. The TLR4 pathway is a common inflammation-related pathways, and while TLR4 is highly expressed in adhesion tissue, the function of TLR4 in adhesion formation remains unclear. In our study, we demonstrated that the TLR4 inhibitor TAK-242 could reduce abdominal adhesion in a mouse model. Methods The expression of TLR4 was examined by immunohistochemical and double-immunofluorescence staining. Forty mice were randomly divided into five groups and treated with different drugs. Seven days after surgery, the mice were sacrificed, and specimens were collected. Inflammation was detected by HE staining and ELISA analysis of TGF-β1 and IL-6, collagen deposition was examined by Masson staining and IHC staining of α-SMA, and ROS were detected by ROS staining and MDA assays. Results TLR4 was highly expressed in adhesion tissue on days 3, 5 and 7 after surgery. TAK-242 plus sodium hyaluronate reduced the abdominal adhesion formation score. TAK-242 decreased the inflammation score and TGF-β1 and IL-6 levels in adhesion tissue, and collagen thickness and α-SMA level were lower than those in the control group. The TAK-242 group had lower ROS and MDA levels than the control group. Conclusions TLR4 was highly expressed in adhesion formation, and its inhibitor TAK-242 reduced adhesion formation by reducing inflammation and ROS and alleviating collagen deposition.