Abstract：
Intestinal ischemia/reperfusion (I/R) injury is a serious condition that causes intestinal dysfunction and can be fatal. Previous research has shown that toll-like receptor 4 (TLR4) inhibitors have a protective effect against this injury. This study aimed to investigate the protective effects of TLR4 inhibitors, specifically cyclobenzaprine, ketotifen, amitriptyline, and naltrexone, in rats with intestinal (I/R) injury. Albino rats were divided into seven groups: vehicle control, sham-operated, I/R injury, I/R-cyclobenzaprine (10 mg/kg body weight), I/R-ketotifen (1 mg/kg body weight), I/R-amitriptyline (10 mg/kg body weight), and I/R-naltrexone (4 mg/kg body weight) groups. Anesthetized rats (urethane 1.8 g/kg) underwent 30 min of intestinal ischemia by occluding the superior mesenteric artery (SMA), followed by 2 h of reperfusion. Intestinal tissue samples were collected to measure various parameters, including malondialdehyde (MDA), nitric oxide synthase (NO), myeloperoxidase (MPO), superoxide dismutase (SOD), TLR4, intercellular adhesion molecule-1 (ICAM-1), nuclear factor kappa bp65 (NF-ĸBP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), macrophages CD68, myeloid differentiation factor 88 (MYD88), and toll interleukin receptor-domain-containing adaptor-inducing interferon β (TRIF). The use of TLR4 inhibitors significantly reduced MDA, MPO, and NO levels, while increasing SOD activity. Furthermore, it significantly decreased TLR4, ICAM-1, TNF-α, MCP-1, MYD88, and TRIF levels. These drugs also showed partial restoration of normal cellular structure with reduced inflammation. Additionally, there was a decrease in NF-ĸBP65 and macrophages CD68 staining compared to rats in the I/R groups. This study focuses on how TLR4 inhibitors enhance intestinal function and protect against intestinal (I/R) injury by influencing macrophages CD86 through (MYD88-TRIF) pathway, as well as their effects on oxidation and inflammation.
摘要：
肠缺血/再灌注(I/R)损伤是导致肠功能障碍的严重病症,并且可以是致命的。先前的研究表明，toll样受体4（TLR4）抑制剂对这种损伤具有保护作用。本研究旨在探讨TLR4抑制剂的保护作用,特别是环苯扎林，酮替芬,阿米替林,和纳曲酮,在大鼠肠（I/R）损伤中。白化病大鼠分为7组：载体对照，假手术,I/R损伤,I/R-环苯扎林（10mg/kg体重），I/R-酮替芬（1mg/kg体重），I/R-阿米替林（10mg/kg体重），和I/R-纳曲酮(4mg/kg体重)组。麻醉大鼠（尿烷1.8g/kg）通过闭塞肠系膜上动脉（SMA）进行肠缺血30分钟，然后再灌注2小时。收集肠组织样本以测量各种参数，包括丙二醛（MDA），一氧化氮合酶（NO），髓过氧化物酶(MPO),超氧化物歧化酶（SOD），TLR4,细胞间粘附分子-1(ICAM-1),核因子κbp65（NF-BP65），单核细胞趋化蛋白-1（MCP-1），肿瘤坏死因子-α(TNF-α),巨噬细胞CD68，髓样分化因子88（MYD88），和Toll含白介素受体结构域的衔接子诱导干扰素β（TRIF）。使用TLR4抑制剂显著降低MDA，MPO,和没有水平，同时增加SOD活性。此外，它显着降低TLR4，ICAM-1，TNF-α，MCP-1、MYD88和TRIF水平。这些药物还显示出部分恢复正常的细胞结构和减少的炎症。此外,与I/R组大鼠相比，NF-BP65和巨噬细胞CD68染色降低。本研究的重点是TLR4抑制剂如何通过（MYD88-TRIF）途径影响巨噬细胞CD86，增强肠道功能并防止肠道（I/R）损伤。以及它们对氧化和炎症的影响。
