Souza Lourenilson J, Shio Marina T, Molan Nilza A T, Machado Marcel C C, Jancar Sonia
Department of Surgery, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Pancreatology. 2007;7(1):67-73. doi: 10.1159/000101880. Epub 2007 Apr 18.
BACKGROUND/AIM: During acute experimental pancreatitis, inflammatory mediators/cytokines are released by the pancreas and enter the portal venous system, reaching the liver. We investigate some aspects of the liver cell function under conditions of acute pancreatitis and the effect of in vivo treatment with a selective platelet-activating factor (PAF) antagonist.
Cells were isolated from Wistar rats 24 h after induction of acute pancreatitis by retrograde injection of sodium taurocholate into the main pancreatic duct. The non-parenchymal cell population was separated by Percoll gradient and the adherent cell population (Kupffer cells) obtained. The cells were cultured for 24 h and supernatants assayed for nitrite by Griess reaction and for tumour necrosis factor (TNF) by bioassay in L929 cells. The microbicidal activity was evaluated by killing of Candida albicans. The PAF antagonist WEB2170 (10 mg/kg i.v.) was administered 30 min before induction of pancreatitis.
We found that liver cells produce nitric oxide (NO) only under lipopolysaccharide stimulation and that WEB-2170 treatment reduces the NO production by liver cells in the pancreatitis group only. Cells from both groups produced TNF spontaneously, and the levels were further increased after lipopolysaccharide stimulation. WEB-2170 treatment did not affect the TNF levels. Moreover, killing of C. albicans by Kupffer cells wassignificantly increased by the PAF antagonist.
These results suggest that PAF released during acute pancreatitis upregulates the NO production by non-parenchymal liver cells and inhibits Kupffer cell microbicidal activity which could explain the increased bacterial dissemination observed in acute pancreatitis.
背景/目的：在急性实验性胰腺炎期间，胰腺会释放炎症介质/细胞因子，这些物质进入门静脉系统，进而到达肝脏。我们研究了急性胰腺炎条件下肝细胞功能的某些方面，以及体内使用选择性血小板活化因子（PAF）拮抗剂治疗的效果。
通过向主胰管逆行注射牛磺胆酸钠诱导Wistar大鼠发生急性胰腺炎24小时后，分离细胞。通过Percoll梯度分离非实质细胞群体，获得贴壁细胞群体（库普弗细胞）。将细胞培养24小时，通过格里斯反应测定上清液中的亚硝酸盐，并通过L929细胞生物测定法测定肿瘤坏死因子（TNF）。通过白色念珠菌的杀灭情况评估杀菌活性。在诱导胰腺炎前30分钟静脉注射PAF拮抗剂WEB2170（10毫克/千克）。
我们发现肝细胞仅在脂多糖刺激下产生一氧化氮（NO），并且WEB-2170治疗仅降低了胰腺炎组肝细胞的NO产生。两组细胞均自发产生TNF，脂多糖刺激后水平进一步升高。WEB-2170治疗不影响TNF水平。此外，PAF拮抗剂显著增强了库普弗细胞对白色念珠菌 的杀灭作用。
这些结果表明，急性胰腺炎期间释放的PAF上调了非实质肝细胞的NO产生，并抑制了库普弗细胞的杀菌活性，这可以解释急性胰腺炎中观察到的细菌播散增加现象。
