Farede Lipopolisakkarit ile Oluşturulan Deneysel Sepsis Modelinde Alfa-7 Nikotinik Reseptör Agonisti PNU-282987’nin, Mezenter-Portal Perfüzyon ve Organ Hasarına Etkileri

Abstract

Sepsis is life-threatening organ dysfunction caused by dysregulated host response to infection. It is among the most common reasons for admission to intensive care units in worldwide. Sepsis is characterized by systemic inflammation and hypoperfusion; it also causes extensive organ damage, including liver and spleen. Tonus and physiological function of the vascular system are heterogeneously impaired by sepsis related response dysregulation. As a result of hypoperfusion, organ damage and dysfunction occur. The cholinergic anti-inflammatory pathway reduces inflammatory responses through vagus nerve stimulation and alpha-7 nicotinic acetylcholine receptor (α7nAChR). In this study, the effects of α7nAChR agonist PNU-282987 on mesenteric artery and portal vein blood flow velocity and liver and spleen damage were investigated in an experimental sepsis model induced by LPS (O111:B4) in mice. PNU-282987 (i.p.) was administered to different groups at the same dose 1 hour before (LPS+PNU-pre) and 1 hour after (LPS+PNU-post) injection of LPS (i.p.) and its therapeutic effects were compared. Blood flow velocity measurements were made under anesthesia 4 hours after LPS injection. Liver and spleen tissue samples were collected for histopathological evaluation and ELISA analysis. TNF-α, IL-1β, TAS and TOS levels were measured to determine oxidative and inflammatory responses. Mesenteric artery blood flow velocity was significantly decreased in LPS treated animals compared to saline group. It increased significantly in the LPS+PNU-pre and LPS+PNU-post groups compared to the LPS group. Portal vein blood flow velocity increased significantly in the LPS+PNU-post group compared to the LPS and LPS+PNU-pre groups. As a result of histopathological examination of liver and spleen samples, it was observed that tissue damage in LPS groups decreased more in the LPS+PNU-post group than in the LPS+PNU-pre group. There was no significant difference between the groups in TNF-α and IL-1β levels. Liver TAS level increased significantly in LPS+PNU-pre and LPS+PNU-post groups compared to LPS group. Splenic TOS level increased significantly in the LPS group compared to the saline group, and decreased significantly in the LPS+PNU-pre group compared to the LPS group. Our results show that the α7nAChR agonist PNU-282987 increases the decreased blood flow velocity in mice with experimental sepsis model, and is effective in correcting the damage in liver and spleen tissue.