Fang Wen-Hui, Yao Yong-Ming, Shi Zhi-Guo, Yu Yan, Wu Ye, Lu Lian-Rong, Sheng Zhi-Yong
Department of Microbiology and Immunology, Burns Institute, 304th Hospital of PLA, Beijing 100037, China.
World J Gastroenterol. 2003 May;9(5):1038-44. doi: 10.3748/wjg.v9.i5.1038.
To investigate changes of tumor necrosis factor-alpha (TNF-alpha) and TNFR-I expression in vital organs and their significance in the pathogenesis of multiple organ damage associated with endogenous endotoxin following major burns.
Wistar rats subjected to a 35 % full-thickness scald injury were sacrificed at 12 h, 24 h, 48 h, and 72 h postburn, respectively. Meanwhile, eight rats were taken as normal controls. Tissue samples from liver, spleen, kidney, lung and intestine were collected to assay tissue endotoxin levels and measure TNF-alpha and TNFR-I expression. In addition, blood samples were obtained for the determination of organ function parameters.
Endotoxin levels in liver, spleen and lung increased markedly after thermal injury, with the highest level in liver. The gene expression of TNF-alpha in liver, lung and kidney was up-regulated after thermal injury, while the TNFR-I mRNA expression in liver, lung, kidney and intestine was shown decreased throughout the observation period. Thus, the mRNA expression ratio of TNF-alpha to TNFR-I was significantly increased postburn, particularly in pulmonary tissue (67-fold). In addition, the significant correlations between the expression of TNFR-I or the expression ratio of TNF-alpha/TNFR mRNA in liver tissue and serum aspartate aminotransferase levels were noted (P<0.05-0.01). Similar results were also obtained between pulmonary TNF-alpha mRNA expression and myeloperoxidase activities (P<0.01), whereas there was a highly negative correlation between levels of renal TNFR-I mRNA expression and serum creatinine.
Burn injury could result in the translocation of gut-derived endotoxin that was mainly distributed in the liver, spleen and lung. The translocated endotoxin then made the expression of TNF-alpha and TNFR-I mRNA up-regulated and down-regulated respectively in various organs, which might be involved in the pathogenesis of multiple organ damage following burns.
探讨重度烧伤后内源性内毒素血症所致多器官损害中，重要脏器肿瘤坏死因子-α（TNF-α）及肿瘤坏死因子受体-I（TNFR-I）表达的变化及其意义。
将Wistar大鼠制成35%总体表面积的Ⅲ度烫伤模型，于伤后12 h、24 h、48 h及72 h分批处死，另取8只大鼠作为正常对照。取肝、脾、肾、肺及小肠组织，检测组织内毒素水平，测定TNF-α及TNFR-I的表达；同时取血检测器官功能指标。
烫伤后肝、脾、肺内毒素水平显著升高，以肝组织最为明显。烫伤后肝、肺、肾组织TNF-α基因表达上调，而肝、肺、肾、小肠组织TNFR-I mRNA表达在观察期内均呈下降趋势，TNF-α与TNFR-I mRNA表达比值伤后显著升高，以肺组织最为明显（67倍）。肝组织TNFR-I表达及TNF-α/TNFR mRNA表达比值与血清天门冬氨酸氨基转移酶水平显著相关（P<0.05~0.01）；肺组织TNF-α mRNA表达与髓过氧化物酶活性显著相关（P<0.01）；肾组织TNFR-I mRNA表达水平与血清肌酐呈高度负相关。
烧伤后可导致肠道源性内毒素移位，主要分布于肝、脾、肺组织。移位的内毒素使各脏器TNF-α及TNFR-I mRNA表达分别上调和下调，这可能参与了烧伤后多器官损害的发病过程。
