油酸/脂多糖致伤老年大鼠MODS的Toll样受体4 mRNA表达变化及意义  

Changes and roles of Toll-like receptor 4 mRNA expression in elderly rats with multiple organ dysfunction syndrome induced with oleic acid and lipopolysaccharide

作　　者：王兴胜[1] 吴国明[1] 钱桂生[1] 徐智[1] 陈维中[1] 李淑平[1] 薛桥[2] 王士雯[2] 

机构地区：[1]第三军医大学新桥医院全军呼吸内科研究所,全军呼吸病研究重点实验室,重庆400037 [2]解放军总医院老年心血管病研究所,北京100853

出　　处：《第三军医大学学报》2005年第7期621-624,共4页Journal of Third Military Medical University

基　　金：国家重点基础研究发展规划资助项目 ("973"项目 ) (G2 0 0 0 0 570 0 4 )~~

摘　　要：目的　观察油酸/脂多糖(OA/LPS)致伤的老年大鼠多器官功能障碍综合征(MODSE)主要脏器组织Toll样受体4(TLR4)mRNA表达变化,探讨TLR4在MODSE发生中的作用。方法　80只SD大鼠分为老年组及青年组,予以油酸(OA ,0 2 5ml/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MODS模型。观察对照组及伤后2、6、2 4h ,重要器官(肺、心、肝、肾)病理及功能的变化,分别检测肺、心、肝和肾组织中TLR4mRNA表达变化。结果　OA/LPS致伤后,肺脏损害出现最早,PaO2 于2h降至最低值,而心、肝、肾功能损害指标于6h达峰值。在同一时相点,老年鼠脏器损害重于青年鼠(P <0 0 5 ,P <0 0 1)。致伤后肺、心、肝和肾组织中TLR4mRNA表达均显著升高(P <0 0 5 ,P <0 0 1) ;其中以肺组织中最高,升高幅度最大,于2h达峰值;心、肝、肾组织中于6h达峰值。在相同时相点老年鼠各组织中TLR4mRNA表达高于青年鼠(P <0 0 5 ,P <0 0 1)。结论　油酸+脂多糖所致老年鼠多器官功能障碍重于青年鼠,以肺损伤出现最早,损伤最重。致伤后大鼠肺、心、肝、肾组织中TLR4mRNA表达升高,老年组高于青年组,以肺组织中最高,升高幅度最大,在MODSE发病机制中起重要作用,可能是MODSE发生过程中肺脏最先且严重受损的原因之一。Objective To study the changes and roles of Toll-like receptor 4 (TLR4) mRNA expression in tissues of elderly rats of multiple organ dysfunction syndrome (MODS) induced with oleic acid (OA) and lipopolysaccharide (LPS). Methods MODS models of young and elderly rats were established by OA (0.25 ml/kg) and LPS (3.5 mg/kg) injected to SD rats with the interval of 4 h. Forty three-month-old SD rats and 40 twenty-month-old SD rats were randomly divided into four groups, respectively: control group (n=10) and OA and LPS groups (n=10 in each group) of 2, 6, and 24 h. The pathomorphological and functional changes of lung, heart, liver and kidney were observed. Semi-quantitative RT-PCR was used to measure mRNA expression of TLR4 in lung, heart, liver and kidney tissues. Results After OA and LPS injected to young rats and to elderly rats, the lung injured first and PaO 2 decreased to minimal level at 2 h. Biochemical indexes of functional lesion of heart, liver and kidney increased to the peak level at 6 h. At the same time points, organs injured more seriously in elderly group than those in young group (P<0.05 or P<0.01). The expression of TLR4 mRNA increased to the peak level in lung tissue at 2 h and in heart, liver and kidney tissues at 6 h after LPS injection (P<0.05 or P<0.01). The expression of TLR4 mRNA increased most in lung tissue. The expressions of TLR4 mRNA of different tissues were higher in elderly group than those in young group at the same time points (P<0.05 or P<0.01). Conclusion OA and LPS injection led to more serious multiple organs injure in elderly rats than in young rats. The lung was first and seriously injured. That TLR4 mRNA expressions increased more in lung, heart, liver and kidney of elderly rats than in those of young rats after OA and LPS injection, and increased most in lung, may play an important role in pathogenesis of the elderly MODS rats.

关 键 词：多器官功能障碍综合征 老年大鼠 油酸 脂多糖 TOLL样受体4 

分 类 号：R392.11[医药卫生—免疫学] R392.2[医药卫生—基础医学]