Volman Thomas J H, Goris R Jan A, van der Meer Jos W M, Hendriks Thijs
Department of Surgery, University Medical Center, Nijmegen, The Netherlands.
Ann Surg. 2004 Jul;240(1):142-50. doi: 10.1097/01.sla.0000130725.52373.e7.
We sought to quantitate the course of specific cytokine mRNA expression in tissues that exhibit increasing histopathological changes in time in an animal model for the multiple organ dysfunction syndrome (MODS).
The development of treatment protocols for MODS requires elucidation of the mechanisms and mediators involved. To devise logical interventions, it is necessary to collect data on cytokine expression at tissue level during the development of MODS.
Ninety-four C57BL/6 mice were given an intraperitoneal injection of 40 microg of lipopolysaccharide (LPS), followed by zymosan at a dose of 0.8 mg/g body weight 6 days later (day 0). Six additional animals did not receive zymosan and acted as controls. At several time points after zymosan injection, 6 randomly assigned, zymosan-treated animals were killed, and their livers, lungs, spleens, and kidneys were collected. mRNA expression of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, macrophage migration inhibiting factor, IL-12, interferon-gamma, and IL-10 was measured using a real-time reverse transcription-polymerase chain reaction assay.
The injection of zymosan induced an acute peritonitis, followed by an apparent recovery. From approximately day 6 onwards, animals started to display MODS-like symptoms. During the peritonitis phase, up-regulation of cytokine mRNA was limited. During the period of apparent recovery, cytokine mRNA expression strongly increased, mostly reaching its maximum at day 9 when deterioration of the clinical condition had already set in. The up-regulation of tumor necrosis factor-alpha mRNA was most pronounced, especially in the lungs and liver.
Interventions should preferentially be targeted against multiple cytokines and, at least in this model, there may be a treatment window well after the initial challenge.
我们试图在多器官功能障碍综合征（MODS）动物模型中，对随时间推移组织病理学变化不断加重的组织中特定细胞因子mRNA表达过程进行定量分析。
MODS治疗方案的制定需要阐明其中涉及的机制和介质。为了设计合理的干预措施，有必要收集MODS发展过程中组织水平细胞因子表达的数据。
94只C57BL/6小鼠腹腔注射40微克脂多糖（LPS），6天后（第0天）再注射剂量为0.8毫克/克体重的酵母聚糖。另外6只动物未注射酵母聚糖作为对照。在注射酵母聚糖后的几个时间点，随机选取6只经酵母聚糖处理的动物处死，收集其肝脏、肺、脾脏和肾脏。采用实时逆转录-聚合酶链反应法检测肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、巨噬细胞移动抑制因子、IL-12、干扰素-γ和IL-10的mRNA表达。
注射酵母聚糖诱发急性腹膜炎，随后明显恢复。从大约第6天起，动物开始出现类似MODS的症状。在腹膜炎阶段，细胞因子mRNA的上调有限。在明显恢复期间，细胞因子mRNA表达强烈增加，大多在第9天达到峰值，此时临床状况已经开始恶化。肿瘤坏死因子-α mRNA的上调最为明显，尤其是在肺和肝脏中。
干预措施应优先针对多种细胞因子，至少在该模型中，初始刺激后可能存在一个治疗窗。
