失血性休克小鼠心肌Toll样受体的表达

Expression of Toll-like receptor in myocardium in mice with hemorrhagic shock

目的:探讨小鼠失血性休克(无复苏)对心肌Toll样受体(toll-likereceptor,TLR)表达变化的影响及其可能的意义。方法:45只C57BL/6的小鼠随机分为3组:失血组、假手术组、脂多糖(LPS)组(尾静脉注射LPS5mg/kg),每组15只小鼠,采用心脏穿刺法建立小鼠失血性休克模型;心肌TLR-2mRNA和TLR-4mRNA的表达利用RT-PCR的方法进行分析;左室收缩功能以测定的左室收缩末压(leftventricularend-systolicpressure,LVESP)作为指标。结果:①与假手术组比较,失血性休克及LPS刺激后小鼠的动脉血压出现下降;②与假手术组比较,失血性休克及LPS刺激后均可导致左室收缩功能障碍;③失血性休克及LPS刺激后TLR2和TLR4基因的表达水平均出现不同程度的上调,而假手术组在各时间点未见明显改变。结论:①失血性休克及LPS刺激后心肌TLR2及TLR4基因表达的上调与心功能障碍存在密切联系,但这两种病理状态下的信号转导通路可能存在差异;②失血性休克和LPS刺激后TLR2、TLR4升高增强了机体的天然免疫能力,提高了机体对急性炎症的应激能力,对机体具有保护作用,但其过度表达也可能对组织、器官功能产生损害。

Objective： To investigate the effect and significance of hemorrhagic shock without resuscitation on expression of toll-like receptor （TLR） in myocardium.Method：Forty-five C57BL/6 mice were randomly divided into three groups： hemorrhage group,sham-operated group,lipopolysaccharide （LPS） group,and there were fifteen mice in each group.The hemorrhagic shock mouse model was developed by heart puncture. Expression levels for TLR2 mRNA and TLR4 mRNA were detected by RT-PCR.Left ventricular end-systolic pressure （LVESP） was determined and adopted as an index of left ventricle contractile function.Result：①Both hemorrhagic shock and LPS challenge could lead to a reduction of arterial pressure in mice when compared with that of sham-operated group. ②Both hemorrhagic shock and LPS challenge could result in left ventricle contractile dysfunction when compared with that of sham-operated group. ③Expression levels for TLR2 and TLR4 genes were upregulated in myoeardium at a different extent after hemorrhagic shock and LPS challenge,in contrast, the changes for that of in sham-operated group was absent.Conclusion：①The upreguahion of TLR2 and TLR4 is closely connected with hemorrhagic shock and LPS-induced left ventricle contractile dysfunction, and there may exist difference in signal transduction pathway between the two pathological conditions. ②The host ability of innate immune response may be reinforced by the upregulation of TLR2 and TLR4, whereas, overexpression of them may also impair the function of tissues or organs.