Nieuwenhuijzen G A, Meyer M P, Hendriks T, Goris R J
Department of Surgery, University Hospital St. Radboud, Nijmegen, The Netherlands.
Crit Care Med. 1995 Oct;23(10):1686-93. doi: 10.1097/00003246-199510000-00013.
To evaluate the role of complement factor C5 in a model of zymosan-induced multiple organ dysfunction syndrome.
Experimental animal study.
Central animal laboratory of a university hospital.
Twenty-five C5-deficient B2D10/Old and 25 C5-sufficient B2D10/New mice.
On day 0, all mice received an intraperitoneal injection with zymosan suspended in paraffin in a dose of 1 mg/g body weight.
Between days 0 and 12, biological parameters (temperature, body weight, and clinical condition) were measured daily and mortality was monitored. Clinical condition was assessed as a symptom score by blindly grading the degree of lethargy, conjunctivitis, diarrhea, and ruffled fur of each mouse on a 2-point scale (maximum score of 4). On day 12, all surviving mice were killed and relative organ weights of lungs, liver, spleen, and kidneys were calculated. Relative organ weight was defined as (organ weight/body weight) x 100%. Zymosan administration induced a typical triphasic illness. Deterioration of the clinical condition, as indicated by the symptom score, and the decrease in temperature and body weight in the acute phase were all significantly less severe in C5-deficient mice (p < .005). In the late phase, no differences could be noticed in the courses of these biological parameters. Overall mortality was 2 (8%) of 25 in C5-deficient mice and 8 (32%) of 25 in C5-sufficient mice (p = .049), a difference that was mainly due to a difference in the acute phase. Organ damage, assessed as the relative organ weights, did not show any statistical differences for any organ between both strains.
Complement factor C5 appears to play an important role in the acute hyperdynamic septic response in this model. However, deficiency of C5 could not prevent organ damage in the late multiple organ dysfunction syndrome phase. This finding suggests that other factors must be more important in the development of the inflammatory response leading to multiple organ dysfunction syndrome.
评估补体因子C5在酵母聚糖诱导的多器官功能障碍综合征模型中的作用。
实验性动物研究。
大学医院的中央动物实验室。
25只C5缺陷型B2D10/Old小鼠和25只C5充足型B2D10/New小鼠。
在第0天，所有小鼠腹腔注射悬浮于石蜡中的酵母聚糖，剂量为1mg/g体重。
在第0天至第12天期间，每天测量生物学参数（体温、体重和临床状况）并监测死亡率。临床状况通过对每只小鼠的嗜睡程度、结膜炎、腹泻和被毛蓬松程度进行盲法2分制评分（最高分为4分）来评估。在第12天，处死所有存活小鼠并计算肺、肝、脾和肾的相对器官重量。相对器官重量定义为（器官重量/体重）×100%。酵母聚糖给药诱导了典型的三相性疾病。C5缺陷型小鼠急性期临床状况的恶化（以症状评分表示）以及体温和体重的下降均明显较轻（p <.005）。在后期，这些生物学参数的变化过程未观察到差异。C5缺陷型小鼠的总体死亡率为25只中的2只（8%），C5充足型小鼠为25只中的8只（32%）（p = 0.049），这种差异主要归因于急性期的差异。以相对器官重量评估的器官损伤在两品系间的任何器官上均未显示出统计学差异。
补体因子C5在该模型的急性高动力性脓毒症反应中似乎起重要作用。然而，C5缺乏并不能预防多器官功能障碍综合征后期的器官损伤。这一发现表明，在导致多器官功能障碍综合征的炎症反应发展过程中，其他因素可能更为重要。
