- 學位論文
麩醯胺對於敗血症免疫調節及器官損傷之影響
Immunoregulation of glutamine on sepsis-induced organ injury in mice
摘要
敗血症是造成加護病房中病人死亡的主要原因之ㄧ，急性腎損傷(acute kidney injury, AKI)與急性肺損傷(acute lung injury, ALI)是敗血症之嚴重併發症，會減緩預後並增加患者死亡率。麩醯胺(glutamine, GLN)為臨床上常使用的免疫調節營養素，且腎臟及肺臟皆為代謝、維持GLN衡定之重要器官。本研究以盲腸節紮穿刺手術(cecal ligation and puncture, CLP)模擬臨床由腹膜炎引致敗血症之小鼠動物模式，於誘發小鼠敗血症後一小時由尾靜脈注射單一劑量GLN (0.75g/body weight)，探討GLN對於敗血症造成之腎及肺損傷發炎及免疫調節機制之影響。研究結果發現，GLN能增加腎臟中熱休克蛋白(heat shock protein, HSP)-70表現以及減少腎臟受到過氧化物之傷害，並降低腎臟中發炎介質high-mobility group box (HMGB)-1/nuclear factor (NF)-κB傳遞路徑相關蛋白質與基因之表現，減緩腎損傷；GLN亦會增加敗血症小鼠循環血和肺部γδ T細胞之比例，影響肺部γδ T細胞內細胞激素分泌、降低γδ T細胞凋亡與嗜中性白血球浸潤，減少肺組織內促發炎細胞激素Interleukin (IL)-23、IL-17、IL-1β之濃度，減緩肺損傷；並增加敗血症小鼠48小時存活率。本研究結果顯示，GLN具有調節敗血症造成之發炎及免疫反應有助於降低敗血症器官病變發生，可做為臨床上敗血症病患使用GLN營養治療之參考依據。
並列摘要
Sepsis is the leading cause of death in critically ill patients, and patients with complications of acute kidney injury (AKI) or acute lung injury (ALI) have worsened survival prognosis and higher mortality rates. Since glutamine (GLN) is a common nutrient used in immunonutrition regimens, and kidney and lung are the important organs for GLN metabolism and homeostasis, we hypothesized that GLN admistration may have anti-inflammatory and immunoregulatory effects and thus ameliorate sepsis-induced AKI and ALI. Sepsis was induced by cecal ligation and puncture (CLP), which is the most closely mimics the clinical conditions of postsurgical peritonitis in human patients. GLN was given 0.75 g/kg body weight once via a tail vein 1 h after CLP. The results showed that a single dose of GLN administered as post‐treatment after the initiation of sepsis was found to decrease expressions of high-mobility group box-1/phosphorylated nuclear factor-κB p65 pathway related proteins/genes and reduce nitrotyrosine levels in kidney tissues as well as ameliorate kidney injury. Besides, GLN enhanced the proportion of γδ T cell subset in lungs, affected γδ T cells cytokine secretion, prevented the apoptosis of γδ T cells and neutrophils infiltration into lungs, reduced interleukin (IL-17)A, IL-1β, and IL-23 concentrations and the micro-architecture damage in the lung. GLN also improved survival at 48 h post-CLP. This study provides basic information and implies that GLN supplementation should be considered for preventing sepsis-induced AKI and ALI.