Sailai Yalikun, Yu Xiao, Baiheti Paerhati, Tang Huayong, Li Yongguo, Xu Ming
Department of Emergent Surgery, First Teaching Hospital of Xinjiang Medical University, Xinjiang Province, China.
J Investig Med. 2010 Jan;58(1):38-42. doi: 10.2310/JIM.0b013e3181b91bd6.
To investigate the potential influence of nuclear factor kappaB (NF-kappaB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate the effect of an inhibitor of NF-kappaB-N-acetylcysteine (NAC).
Ninety male Sprague-Dawley rats were randomly divided into 3 groups, 30 of each: control, ANP, and ANP plus NAC groups. The ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. In addition to sodium taurocholate, the ANP plus NAC group received intravenous infusion of NAC (25 mg/100 g). At the sixth hour after modeling, the protein content of the bronchoalveolar lavage fluid, the myeloperoxidase in the lung tissue, and the transforming growth factor alpha and the nitric oxide (NO) secreted by AMs were determined. The histopathologic changes of the pancreas and the lung were observed under light microscope, and NF-kappaB activation of AMs was detected.
The protein content of the bronchoalveolar lavage fluid and the myeloperoxidase level of the lung tissue showed a significant increase in the ANP group as compared with the NAC-administered group. The levels of transforming growth factor alpha and NO secreted by AMs in the ANP and the ANP plus NAC group rose significantly over that in the control group, and there was a significant difference between them. Although they were still higher than those in the control group, the pancreas destruction and the lung injury were slighter in the ANP plus NAC group and the activation of NF-kappaB was lower in the ANP plus NAC group as compared with that in the ANP group.
The correlation between the NF-kappaB activation, the up-regulation of the inflammatory mediators secreted by AMs, and the tissue damage suggests a key influence of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the lung injury of ANP.
探讨核因子κB（NF-κB）激活对急性坏死性胰腺炎（ANP）大鼠肺泡巨噬细胞（AMs）分泌炎症介质的潜在影响，并评估NF-κB抑制剂N-乙酰半胱氨酸（NAC）的作用。
90只雄性Sprague-Dawley大鼠随机分为3组，每组30只：对照组、ANP组和ANP加NAC组。通过向胰管逆行注射5%牛磺胆酸钠建立ANP大鼠模型。除牛磺胆酸钠外，ANP加NAC组静脉输注NAC（25mg/100g）。建模后第6小时，测定支气管肺泡灌洗液蛋白含量、肺组织髓过氧化物酶、AMs分泌的转化生长因子α和一氧化氮（NO）。在光学显微镜下观察胰腺和肺的组织病理学变化，并检测AMs的NF-κB激活情况。
与给予NAC的组相比，ANP组支气管肺泡灌洗液蛋白含量和肺组织髓过氧化物酶水平显著升高。ANP组和ANP加NAC组AMs分泌的转化生长因子α和NO水平均显著高于对照组，且两组间有显著差异。尽管ANP加NAC组仍高于对照组，但与ANP组相比，其胰腺破坏和肺损伤较轻，NF-κB激活程度较低。
NF-κB激活、AMs分泌炎症介质上调与组织损伤之间的相关性表明NF-κB在ANP发病机制中起关键作用。抑制NF-κB激活可能逆转ANP的肺损伤。
