髓样细胞触发受体-1（TREM-1）在大肠埃希菌诱导新生大鼠败血症中的意义
发布时间：2018-12-11 07:04
【摘要】：目的:败血症是临床常见重症之一,为感染后所致的全身炎症反应综合症。新生儿对各种病原微生物易感性高,极易引起败血症,且病死率很高,败血症的早期诊断、及时合理治疗是目前临床所需迫切面对的问题。固有免疫是一种天然免疫系统,是机体抵御病原体感染的第一道防线。巨噬细胞是机体固有免疫系统的重要一员,其功能状态直接影响到感染的预后。髓样细胞触发受体-1(Triggering receptor expressed on myeloid cells-1,TREM-1)选择性表达于中性粒细胞、单核巨噬细胞表面,能够促进TNF-α、IL-1β等细胞因子的表达,具有激发和放大炎症反应的作用,其可溶性的形式sTREM-1存在于体液中,共同参与炎症反应,发挥抗炎作用。本课题通过建立新生大鼠大肠埃希菌败血症模型来分析组织巨噬细胞表面TREM-1的表达情况以及外周血中sTREM-1水平的变化,来探讨TREM-1在新生大鼠败血症发病机制中的作用,并尝试开拓败血症免疫调控干预的新思路。 方法:选择无特定病原体(SPF级)7日龄Sprague-Dawley(SD)大鼠72只,体重16-20g,雌雄不限,分成对照组和败血症组,每组36只。所有动物按照随机的原则分入两组不同的时间点,即实验后第2、4、8、12、24、48小时六个时间点,每个时间点为6只新生大鼠。采用腹腔注射大肠埃希菌(E.coli)方法建立败血症模型,对照组则用等量生理盐水腹腔注射。于各目标时间点麻醉动物后,心脏采血,再留取肝脏、肺脏于福尔马林液中固定备用。选择免疫组织化学法分析肝脏、肺脏巨噬细胞表面TREM-1的表达情况,ELISA法检测血浆中sTREM-1的水平。 结果:1.对照组新生大鼠肝、肺组织中巨噬细胞表面TREM-1和血浆中sTREM-1各时间点表达水平均无显著性差异(P0.05);2.败血症组新生大鼠肝、肺组织中巨噬细胞表面TREM-1和血浆中sTREM-1的表达水平,均随着实验时间的延长而逐渐升高,于12小时左右达高峰,后有所下降,但至48小时仍维持在较高水平;3.实验进展至2小时,败血症组肝、肺组织中巨噬细胞表面TREM-1表达及血浆中sTREM-1浓度分别与对照组比较均无显著性差异(P0.05);实验进展至4小时及以后,败血症组高于对照组水平,差异有显著统计学意义(P0.01)。 结论:1.随着实验进展,败血症组和对照组新生大鼠肝、肺组织巨噬细胞表面TREM-1表达水平和血浆中sTREM-1浓度均存在显著性差异,说明TREM-1在败血症发病机制中具有重要作用。2.败血症组新生大鼠组织巨噬细胞表面TREM-1分子表达水平随着败血症的进展,呈时间依赖性升高,提示促炎反应加剧;而血浆中sTREM-1浓度亦升高,提示机体抗炎反应亦增强。3.巨噬细胞表面TREM-1和血浆中sTREM-1水平呈平行同向变化,是机体促炎反应和抗炎反应力争达到动态平衡的重要标志之一。4.据此,TREM-1可作为败血症诊断的一种新标志物,并尝试开拓败血症免疫调控干预的新思路。
[Abstract]:Objective: septicemia is one of the common clinical severe cases, which is caused by systemic inflammatory response syndrome. Newborns are susceptible to various pathogens and are prone to septicemia, and the mortality is very high. The early diagnosis and timely and reasonable treatment of septicemia are urgent problems that need to be faced in clinical practice. Innate immunity is a innate immune system and the first line of defense against pathogen infection. Macrophages are important members of the innate immune system, and their functional status directly affects the prognosis of infection. Myeloid cell trigger receptor-1 (Triggering receptor expressed on myeloid cells-1,TREM-1) is selectively expressed on the surface of neutrophils and mononuclear macrophages, which can promote the expression of cytokines such as TNF- 伪 and IL-1 尾. The soluble form of sTREM-1 exists in the body fluid and participates in the inflammatory reaction and plays an anti-inflammatory role. In this study, we established a septicemia model of Escherichia coli in neonatal rats to analyze the expression of TREM-1 on macrophages and the changes of sTREM-1 level in peripheral blood. To explore the role of TREM-1 in the pathogenesis of septicemia in neonatal rats, and try to explore a new idea of immune regulation and intervention in septicemia. Methods: 72 Sprague-Dawley (SD) rats of 7 days age without specific pathogens (SPF grade) were divided into control group and septicemia group with 36 rats in each group. All the animals were divided into two different time points according to the principle of randomness, that is, the 2nd hour, 812h, 24h, 48h after the experiment, each time point was 6 newborn rats. The septicemia model was established by intraperitoneal injection of Escherichia coli (E.coli), while the control group was injected intraperitoneally with the same amount of normal saline. After anaesthetized animals at each target time point, blood was taken from the heart, liver was taken and lung was fixed in formalin solution. The expression of TREM-1 on the surface of hepatic and pulmonary macrophages was analyzed by immunohistochemical method and the level of sTREM-1 in plasma was detected by ELISA method. Results: 1. There was no significant difference in the expression of TREM-1 on the surface of macrophages and sTREM-1 in plasma at different time points in the control group (P0.05). In septicemia group, the expression of TREM-1 on the surface of macrophages and sTREM-1 in plasma increased gradually with the prolongation of experimental time, and reached its peak at about 12 hours, and then decreased. However, it remained at a relatively high level at 48 hours. 3. When the experiment progressed to 2 hours, there was no significant difference in the expression of TREM-1 on the surface of macrophages and the concentration of sTREM-1 in plasma between the septicemia group and the control group (P0.05). The level of septicemia was significantly higher in septicemia group than that in control group after 4 hours (P0.01). Conclusion: 1. With the progress of the experiment, there were significant differences in the expression of TREM-1 on the surface of macrophages and the concentration of sTREM-1 in plasma between the septicemia group and the control group. It is suggested that TREM-1 plays an important role in the pathogenesis of sepsis. 2. In septicemia group, the expression of TREM-1 molecules on macrophages in neonatal rats increased in a time-dependent manner with the progression of septicemia, suggesting that the pro-inflammatory response was aggravated. The concentration of sTREM-1 in plasma was also increased, indicating that the anti-inflammatory response was also increased by 3. 3%. The changes of TREM-1 on macrophage surface and sTREM-1 level in plasma are parallel, which is one of the important markers of pro-inflammatory and anti-inflammatory response to achieve dynamic balance. Therefore, TREM-1 can be used as a new marker in the diagnosis of septicemia, and try to develop a new idea of immune regulation and intervention in septicemia.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363
本文编号：2372108
[Abstract]:Objective: septicemia is one of the common clinical severe cases, which is caused by systemic inflammatory response syndrome. Newborns are susceptible to various pathogens and are prone to septicemia, and the mortality is very high. The early diagnosis and timely and reasonable treatment of septicemia are urgent problems that need to be faced in clinical practice. Innate immunity is a innate immune system and the first line of defense against pathogen infection. Macrophages are important members of the innate immune system, and their functional status directly affects the prognosis of infection. Myeloid cell trigger receptor-1 (Triggering receptor expressed on myeloid cells-1,TREM-1) is selectively expressed on the surface of neutrophils and mononuclear macrophages, which can promote the expression of cytokines such as TNF- 伪 and IL-1 尾. The soluble form of sTREM-1 exists in the body fluid and participates in the inflammatory reaction and plays an anti-inflammatory role. In this study, we established a septicemia model of Escherichia coli in neonatal rats to analyze the expression of TREM-1 on macrophages and the changes of sTREM-1 level in peripheral blood. To explore the role of TREM-1 in the pathogenesis of septicemia in neonatal rats, and try to explore a new idea of immune regulation and intervention in septicemia. Methods: 72 Sprague-Dawley (SD) rats of 7 days age without specific pathogens (SPF grade) were divided into control group and septicemia group with 36 rats in each group. All the animals were divided into two different time points according to the principle of randomness, that is, the 2nd hour, 812h, 24h, 48h after the experiment, each time point was 6 newborn rats. The septicemia model was established by intraperitoneal injection of Escherichia coli (E.coli), while the control group was injected intraperitoneally with the same amount of normal saline. After anaesthetized animals at each target time point, blood was taken from the heart, liver was taken and lung was fixed in formalin solution. The expression of TREM-1 on the surface of hepatic and pulmonary macrophages was analyzed by immunohistochemical method and the level of sTREM-1 in plasma was detected by ELISA method. Results: 1. There was no significant difference in the expression of TREM-1 on the surface of macrophages and sTREM-1 in plasma at different time points in the control group (P0.05). In septicemia group, the expression of TREM-1 on the surface of macrophages and sTREM-1 in plasma increased gradually with the prolongation of experimental time, and reached its peak at about 12 hours, and then decreased. However, it remained at a relatively high level at 48 hours. 3. When the experiment progressed to 2 hours, there was no significant difference in the expression of TREM-1 on the surface of macrophages and the concentration of sTREM-1 in plasma between the septicemia group and the control group (P0.05). The level of septicemia was significantly higher in septicemia group than that in control group after 4 hours (P0.01). Conclusion: 1. With the progress of the experiment, there were significant differences in the expression of TREM-1 on the surface of macrophages and the concentration of sTREM-1 in plasma between the septicemia group and the control group. It is suggested that TREM-1 plays an important role in the pathogenesis of sepsis. 2. In septicemia group, the expression of TREM-1 molecules on macrophages in neonatal rats increased in a time-dependent manner with the progression of septicemia, suggesting that the pro-inflammatory response was aggravated. The concentration of sTREM-1 in plasma was also increased, indicating that the anti-inflammatory response was also increased by 3. 3%. The changes of TREM-1 on macrophage surface and sTREM-1 level in plasma are parallel, which is one of the important markers of pro-inflammatory and anti-inflammatory response to achieve dynamic balance. Therefore, TREM-1 can be used as a new marker in the diagnosis of septicemia, and try to develop a new idea of immune regulation and intervention in septicemia.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363
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