Effects of thymosin β4 on a rat model of severe acute pancreatitis

Abstract

Abstract. The aim of the present study was to investigate the effects of thymosin β4 on a rat model of severe acute pancreatitis (SAP) induced by sodium taurocholate (STC) and the underlying mechanism. SAP was induced by the retrograde infusion of 5% STC (1 ml/kg) into the bile-pancreatic duct. In certain rats, thymosin β4 (30 mg/kg) was administered intraperitoneally 30 min prior to the infusion of STC. The severity of pancreatitis was evaluated by the measurement of serum amylase, lipase, tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase (MPO) levels, and histological grading. Nuclear factor (NF)-κB activation was evaluated by immunohistochemistry and western blot analysis. Intercellular adhesion molecule (ICAM)-1 protein expression in the pancreas was studied using western blot analysis. Prophylactic administration of thymosin β4 was found to attenuate serum amylase and lipase activity and the serum concentrations of proinflammatory cytokines. In addition, it attenuated pathological pancreatic injury, pancreatic MPO activity, and the activation of NF-κB and ICAM-1 in the pancreas. These results suggest that thymosin β4 exerts a protective effect against STC-induced pancreatic injury. IntroductionAcute pancreatitis is an inflammatory disease of the pancreas characterized by acute abdominal pain and increased concentrations of serum amylase and lipase. In the majority of cases, it runs a mild course without complications. However, ~25% patients develop severe acute pancreatitis (SAP), which may result in systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome, and the mortality rate is up to 40% (1,2). In recent years, many investigators have attempted to reveal the pathogenesis of acute pancreatitis; however, the exact mechanisms are not well understood. Accumulating evidence indicates that SAP is closely associated with tissue injury and microcirculation disorders resulting from the production of proinflammatory cytokines and mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and intercellular adhesion molecule (ICAM)-1 (3,4). In addition, studies have shown that acute pancreatitis can lead to activation of the nuclear factor (NF)-κB signaling pathway (5,6). Therefore, reducing the levels of proinflammatory cytokines and adhesion molecules to block the inflammatory cascade may be a valid treatment strategy for acute pancreatitis.Thymosin β4 is a highly conserved polypeptide that was originally isolated from bovine thymus gland extract in 1981 (7). Thymosin β4 contains 43-amino acid residues with a molecular weight of 4964.5 Da and an isoelectric point of 4.6 (8). It is widely distributed in many tissues and cell types and is found in high concentrations in blood platelets, macrophages and white blood cells, but not in red blood cells (9). The most prominent physiological role of thymosin β4 as the major actin-sequestering peptide contributes to the regulation of actin polymerization in mammalian nucleated cells (10). There is g...

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

“…Numerous researchers have endeavored to elucidate the pathogenesis of AP; moreover, the precise molecular mechanisms still need to be understood. Growing evidence suggests that SAP is intricately linked to tissue damage and disturbances in microcirculation, which arise from the release of proinflammatory cytokines and mediators such as TNF-α, IL-1β, IL-6, and intercellular adhesion molecule (ICAM)-1 ( He et al, 2015 ). Experiments have shown that infiltrating inflammatory cells is crucial to experiment-induced AP by producing inflammatory mediators such as IL-1β and monocyte chemoattractant protein-1 (MCP-1) ( Shen et al, 2018 ).…”