TLR-4在多器官功能障碍综合征大鼠肺组织表达的变化及意义  

Expression of TLR4 of Lung in Rat with Multiple Organ Dysfunction Syndrome

作　　者：滕林[1] 余旻[2] 李俊明[2] 余静[1] 江建立[1] 刘先哲[2] 

机构地区：[1]三峡大学医学院 [2]湖北省宜昌市第一人民医院心内科,宜昌443002

出　　处：《实用医学进修杂志》2009年第1期28-32,共5页Journal of Practical Training of Medicine

摘　　要：目的：检测TOLL样受体4（TLR4）在多器官功能障碍综合征大鼠肺组织中表达的变化，探讨其与肺组织中血栓调节蛋白（TM）和基质金属蛋白酶9（MMP-9）表达的关系。方法：雄性SD大鼠采用二次打击建立MODS模型，随机分为正常对照组和MODS模型6h，12h，24h，48h组，不同时相点处理动物。肉眼、光镜观察肺组织的形态结构变化；流式细胞技术（FCM）检测TLR4蛋白表达；免疫组化法测定TM和MMP-9蛋白表达。结果：①正常对照组肺组织结构无改变；MODS组肺组织损伤较重；②与对照组比较，造模后6h肺组织TLR4的表达显著增高，12h达到高峰，24-48h开始下降；③与对照组相比，肺组织TM的阳性表达6h组有所增加，12h达到高峰，随后24-48h下降，至48h与正常对照组TM的阳性表达无显著性差异。肺组织MMP-9的阳性表达6～48h组均比正常对照组有所增加。结论：在MODS肺组织发生病变的早期，TLR4表达上调，TLR4的激活可能通过促进多种炎性因子的分泌损伤肺内皮细胞和基质，TLR4可能参与了MODS后肺组织损伤的病理生理过程，有可能成为治疗MODS的新靶点。Objective： To investigate the expression of toll - like receptor - 4 （TLR4） in the lung of the Multiple Organ Dysfunction Syndrome （MODS） model of rats, evaluate the relationship of its expression with thrombomodulin （TM） and matrix metalloproteinase-9（MMP-9）. Methods： Male SD rats were used the second hits to establish the MODS animal model, and were randomized to two groups： normal control group and MODS model group. The model group were derided into 6 h, 12 h,24 h,48 h four groups. The rats were treated according to different time points. The histological changes in the lung of the rats in all groups were observed by naked eye and light microscope. The expression of TLR4 protein was measured by flow cytometry（FC）. TM and MMP-9 protein expression were deteeeted by immunohistochemistry. Results： （1）There was no change in normal control group, the lung injury was serious in MODS group. （2）Compared with the control group, the lung of TLR4 increased obviously in 6h, peaking at 12hours, then decreased in 24 -48 h. （3）Compared with the control group, the expression levels of TM in lung in 6h increased, peaking at 12hours, then decreased in 24 -48 h. It has no significant difference in 48h. The expression levels of MMP-9 in lung in 6 - 48 h all have significantly increase. Conclusions： In the early lesions of the MODS lung tissue, TLR4 expressed up, the activated TLR-4 may be through promoting the production of a variety of nflammatory factors to damage the lung skin cells and matrix, TLR4 may be involved in the pathogenesis of MODS injury, may become the new therapeutic target of MODS.

关 键 词：多器官功能障碍综合征 TOLL样受体4 血栓调节蛋白 基质金属蛋白酶-9 

分 类 号：R59[医药卫生—内科学] R135.2[医药卫生—临床医学]