致炎细胞因子在两次打击大鼠所致多器官功能障碍综合征中的变化

Changes of inflammatory cytokines in rats with multiple organ dysfunction syndrome induced by a harmful two-hit

目的 通过建立两次打击大鼠所致多器官功能障碍综合征（MODS）的动物模型，探讨致炎细胞因子肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）在MODS的发生、发展中的可能作用。方法 选择清洁级SD大鼠，随机分为正常对照组（32只，A组）、出血＋腹腔注射内毒素组（42只，B组）、出血组（42只，C组）、腹腔注射内毒素组（D组，42只）。在实验的第8小时、24小时、48小时随机抽取每组大鼠各8只，采用放射免疫分析法检测两次打击致伤大鼠在不同时点TNF-α、IL-6的变化，采用免疫组织化学法观察TNF-α阳性细胞在实验大鼠肺组织的表达。结果 在本研究中，B组TNF-α、IL-6水平与A组比较明显增高，差异极具统计学意义（P〈0．01），与C、D组比较也有统计学差异（P〈0．05）。TNF-α在实验8h时升高最为显著，IL-6则在实验24h时达高峰，各指标变化在48h逐渐恢复。免疫组化显示B组肺组织内TNF-α组化在实验后8h呈强阳性表达，而A组呈阴性表达。血清TNF-α、IL-6变化的水平与肺组织病理变化及TNF-α在肺组织内表达相一致。结论 TNF-α、IL-6是MODS早期释放的致炎细胞因子，在MODS的发生、发展中起非常重要的作用。动态监测致炎细胞因子TNF-α、IL-6水平的变化，对评价病情的严重程度及提出有效的防治措施有重要意义。

Objective To study the roles of in inflammatory cytokines tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）） in rat models of multiple organ dysfunction syndrome （MODS）. Method SD rats were randomly divided into four groups. Rats in group A didn＇t receive harmful hits （ n = 32） ; rats in group B were bleeding for 4 hours followed by lipopolysaccharide （endotoxin） injection （ i.p. ） （ Hemorrhagic ＋ endotoxic shocks, n = 42） ; rats in group C were bleeding for 4 hours only （ Hemorrhagic shock, n = 42） ; rats in group D received endotoxin injection （i.p.） only （ Endotoxin shock, n = 42）. After hits were given, eight rats from each group were examined at 8 hours, 24 hours, and 48 hours. The levels of serum TNF-α and IL-6 were measured by radioimmunoassay （RIA）, and tissue samples from lungs were collected to examine the expression of TNF-α by immunohistochemistry. Results All samples showed the contents of TNF-α and IL-6 in group B were higher than those in group C and group D （P 〈0.05）, and also significandy higher those that in group A （P 〈0.01）. The peak levels of TNF-α were found at 8 hours, but IL-6 was seen at 24 hours after two hits. Immunohistochemistry showed that the expression of TNF-α in lungs was strongly positive in group B, but it was negative in group A. In this study, the changes of serum TNF-α and IL-6 were coincided with the variation of pathology in the lungs and the pulmonary expressions of TNF-α. Conclusions TNF-α and IL-6 were the major inflammatory eytokines released in the early phase of MODS, and played an important role in the delayed-development of it. Monitoring the levels of TNF-α and IL-6 may offer a significant information to predict the severity of MODS and guid the treatment.