摘要
目的探讨Toll样受体4基因（TLR4）与TNF-α在老年大鼠多器官功能障碍综合征（MODSE）发病机制中的作用.方法20月龄和3月龄SD大鼠各40只,分别设为老年组及青年组,予油酸（OA）0.25ml/kg和脂多糖（LPS）3.5mg/kg分次静脉注射（间隔4h）,建立二次打击MODSE和青年多器官功能障碍综合征（MODSY）模型.观察对照组及伤后2、6、24h肺、心、肝、肾的病理改变及功能变化,检测肺、心、肝和肾组织中TLR4 mRNA表达及TNF-α含量.结果OA/LPS二次致伤能够导致青年及老年鼠MODS,其中肺脏损害出现最早最重,在同一时相点,老年鼠脏器损害重于青年鼠（P＜0.05～0.01）.致伤后肺、心、肝和肾组织中TLR4 mRNA表达均显著升高（P＜0.05～0.01）,以肺组织中表达最高,2h达峰值,心、肝、肾组织中于6h达峰值;各组织中TNF-α含量均显著升高（P＜0.05～0.01）,以肺组织中升幅最大.在相同时相点老年鼠各组织中TLR4 mRNA表达及TNF-α含量高于青年鼠（P＜0.05～0.01）.结论OA/LPS致伤后老年鼠肺组织中TLR4 mRNA表达及TNF-α水平迅速升高,在MODS发病机制中起重要作用,有可能是MODSE过程中肺损伤出现最早最重的重要原因.
Objective To explore the role of expression of toll-like receptor 4 （TLR4） gene and tumor necrosis factor alpha（TNF-α） in model of multiple organ dysfunction syndrome in the elderly rats （MODSE）. Methods Models of MODSE and models of multiple organ dysfunction syndromes in the young （MODSY） were established by injection of oleic acid（OA） （0.25ml/kg） and LPS （3.5mg/kg） to SD rats （4 hours interval）. Forty three-month-old SD rats and 40 twenty-month-old SD rats were randomly divided into four groups., control group, 2h, 6h, and 24h groups （n= 10 for each group）. The changes of pathomorphology and function of lung, heart, liver and kidney were observed. Semi-quantitative reverse transcription polymerase chain reaction was used to measure TLR4 mRNA levels in lung, heart, liver and kidney tissues. The TNF-α concentrations in those tissues were determined with enzyme linked immunosorbent assay . Results Injection of OA and LPS could lead to MODSE and MODSY. The lung in jury emerged first and was most serious. Dysfunction of organs was more serious in elderly groups than in young groups at the same time points （P〈0.05-0.01）. The TLR4 mRNA levels in lung, heart, liver and kidney tissues increased significantly after injection of OA and LPS （P〈0.05 -0.01）. The expression of TLR4 mRNA increased most markedly and reached peak level in lung in 2h group and in other organs in 6h group. The concentrations of TNF-α in all tissues increased significantly after injection of OA and LPS （P〈0.05-0.01）. The TLR4 mRNA levels and TNF-α concentrations in tissues were higher in elderly groups than in young groups at the same time points （P〈0.05-0.01）. Conclusions The TLR4 mRNA levels and TNF-α concentrations increase irnmediatedly in the lung of elderly rats after injection of OA and LPS, which may explain why the lung injury emerged first and was most serious in MODSE.
出处
《中华老年多器官疾病杂志》
2006年第2期119-123,共5页
Chinese Journal of Multiple Organ Diseases in the Elderly
基金
国家重点基础研究发展规划资助项目("973"项目)(G2000057004)
