目的 探讨Toll样受体4(TLR4)在老龄大鼠感染性多器官损伤发病中的意义.方法 将大鼠分为老龄对照组、老龄模型组和青年对照组、青年模型组；选用气管插管法注入肺炎克雷伯杆菌,由肺炎导致多器官损伤；采用免疫组织化学和分子生物学技术,观察肺、心、小肠组织TLR4样受体信号转导通路主要相关分子表达变化.结果 老龄模型组和青年模型组肺、心、小肠组织内毒素结合蛋白(LBP)、CD14、TLR4、白介素-1受体相关激酶(IRAK) mRNA和TLR4、肿瘤坏死因子受体相关因子-6(TRAF-6)、核因子-kB(NF-κB)阳性细胞数和/或光密度表达分别较老龄对照组和青年对照组明显增强(P＜0.01或P＜0.05),老龄模型组肺、心、小肠组织TLR4和NF-κB分子表达又较青年模型组增高显著(P＜0.01或P＜0.05).结论 TLR4信号转导介导了老年感染性多器官损伤,并发挥了重要作用.%Objective To explore the roles of Toll like receptor 4 (TLR4) in the infectious multiple organ injury in the aged rats. Methods Male SD rats were selected and the young rats were randomly divided into young control ( YCG, re = 10) and model groups ( YMG, n = 15 ) , the elderly rats were divided into aged control ( ACG, n = 10 ) and model groups ( AMG, n = 25 ). The model was duplicated through the tracheal intubation, injecting with Klebsiella pneumoniae. And immunohistochemistry and molecular biology techniques were performed to detect expressions of the molecules, which mainly associate to toll like receptor signaling pathway, in the lung, heart and the small intestine in the multiple organ injury. Results The expressions of lipopolysaccharide-binding protein (LBP) , CD14, TLR4 and I-RAK1 mRNA (interleukin-1 receptor-associated kinase ) were enhanced obviously in the lung, heart and the small intestine tissue in YMG and AMG ( P < 0. 01 or P < 0. 05) , as well as the counts of positive cells and/or the levels of expressions of the integrating optical density of TLR4, TNF receptor-associated factor 6 (TRAF6) and nuclear factor kB ( NF-kB ) were increased (P < 0. 01 or P < 0. 05). At the same time, the expressions of TLR4 and NF-kB in the lung, heart and the small intestine tissues in the AMG were much higher than those in YMG (P <0. 01 or P <0. 05). Conclusions Toll like receptor signaling may take part in the process of infectious multiple organ injury in the elderly and plays an important role.
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