蓝斑核激活与卒中后免疫抑制相关性研究

发布时间：2018-05-23 13:35

本文选题：卒中后免疫抑制 + 蓝斑核　；参考：《东南大学》2015年硕士论文

【摘要】：背景：近年来,脑卒中临床治疗得到飞速发展,脑卒中患者的治愈率和康复率明显提高,但是脑卒中治疗中仍存在一些悬而未决的临床难题,其中卒中相关性感染(stroke-associated infection, SAI)备受人们关注。感染是急性重症脑卒中患者最为常见并发症,发生率高达21～65%,以肺炎和泌尿系感染多见,临床中往往难于控制,常导致病情急骤恶化,妨碍脑卒中原发病症的早期控制和功能康复。卒中相关感染被认为是病情恶化和死亡的独立危险因素,给患者及其家庭带来沉重的负担,已成为当前神经病学领域重大而亟待解决的临床难题。目前卒中后免疫抑制机制主要有四种：原位炎症反应、HPA轴假说、交感神经通路假说,我们前期研究已证明卒中后免疫抑制与交感神经通路激活具有相关性,而交感神经系统的起源是蓝斑核,应激反应可激活蓝斑核内神经元,增强去甲肾上腺素的合成和分泌,以参与唤醒与警戒,而且能增强前额叶的认知功能,提高动机水平,进而提高交感神经活动。本文主要针对蓝斑核激活与卒中后免疫抑制相关性进行研究。目的：深层次地了解脑卒中后感染的生物学发生机制,将有助于寻找临床有效且针对性强的治疗方法,最终提高脑卒中患者整体预后。方法：1、分组：MCAO组(线栓法制作大脑中动脉闭塞模型)、DSP-4+MCAO组(使用神经毒素DSP-4化学性破坏脑内蓝斑核后制作大脑中动脉闭塞模型)、假手术组。2、应用ELISA方法研究假手术组、DSP-4+MCAO组、MCAO组血清中炎症指标：IL-10、TNF-α INF-γ的浓度。3、应用western-blot方法研究假手术组、DSP-4+MCAO组、MCAO组脾脏中NF-κB的蛋白表达4、数据采用GraphPad Prism 5、SPSS软件进行统计学分析,应用Excel绘制图,各指标以均数士标准差(X±S)表示,两组间的均值比较采用配对t检验,多组间资料采用方差分析；所有实验重复三次,以P0.05为差异有统计学意义结果：1、在外周血中,1L-10浓度：假手术组(7.726±0.8492ng/L)、DSP-4+MCAO组(8.153±0.8895 ng/L)及 MCAO组(10.00±0.2034ng/L)具有统计学差异P值=0.0136。TNF-α浓度：假手术组(6.457±0.3743ng/L)、DSP-4+MCAO 组 (6.433±0.7508ng/L)及MCAO组(5.140±0.4986ng/L)具有统计学差异P值=0.0011。INF-γ浓度：假手术组(7.177±0.6336ng/L)、DSP-4+MCAO组(7.291±0.9511 ng/L)及MCAO组(5.882±0.5820ng/L)具有统计学差异P值=0.0068。2、脾脏中NK-κB运用蛋白表达：假手术组及DSP-4+MCAO组术后第1、2、3天,NF-κB蛋白表达无明显差异,MCAO组相对于假手术组NF-κB蛋白表达显著降低。结论：1、MCAO组大鼠相对于假手术组外周血中促炎因子明显降低,抗炎因子明显升高,出现明显免疫激活现象；而DSP-4+MCAO组大鼠相对于假手术组外周血中促炎因子、抗炎因子浓度无显著变化。2、脾脏中NF-κB细胞因子蛋白表达MCAO组相对于假手术组蛋白表达明显降低,DSP-4+MCAO组相对于假手术组无明显差异。
[Abstract]:Background: in recent years, the clinical treatment of stroke has developed rapidly, the cure rate and rehabilitation rate of stroke patients have increased significantly, but there are still some outstanding clinical problems in the treatment of stroke. Among them, Stroke-associated infection (SAI) has attracted much attention. Infection is the most common complication in patients with acute and severe stroke. The incidence of infection is as high as 21 to 65. Pneumonia and urinary tract infections are more common and are often difficult to control in clinical practice, often leading to the rapid deterioration of the condition. It hinders the early control and functional rehabilitation of stroke. Stroke-related infection is regarded as an independent risk factor for the deterioration and death of the disease and brings a heavy burden to the patients and their families. It has become a major and urgent clinical problem in the field of neurology. At present, there are four main mechanisms of poststroke immunosuppression: in situ inflammatory response hypothesis, HPA axis hypothesis and sympathetic pathway hypothesis. Our previous studies have shown that poststroke immunosuppression is related to the activation of sympathetic nerve pathway. The origin of sympathetic nerve system is the nucleus coeruleus. The stress response can activate neurons in the nucleus coeruleus, enhance the synthesis and secretion of norepinephrine, participate in arousal and alert, and enhance the cognitive function and motivation level of prefrontal lobe. And then improve sympathetic activity. The relationship between the activation of locus coeruleus and post-stroke immunosuppression was studied. Objective: to deeply understand the biological mechanism of post-stroke infection, which will help to find effective and targeted treatment methods and improve the overall prognosis of stroke patients. Methods: 1, divided into two groups: MCAO group (middle cerebral artery occlusion model: DS-P-4 MCAO group) (middle cerebral artery occlusion model was made by using neurotoxin DSP-4 after chemical destruction of nucleus coeruleus, sham-operation group .2. ELISA method was used to study prosthetic hand. The concentration of TNF- 伪 INF- 纬 in serum of MCAO group was measured by western-blot method. The expression of NF- 魏 B protein in spleen of MCAO group was studied by western-blot method. The results were analyzed by GraphPad Prism 5- SPSS software. Using Excel to draw the graph, each index is expressed as the mean standard deviation X 卤S, the mean value of the two groups is compared by paired t test, and the data of many groups are analyzed by ANOVA, all the experiments are repeated three times, There were significant differences between the two groups (P < 0.05). There were significant differences in the concentration of 1L-10 in peripheral blood between the sham operation group (7.726 卤0.8492ng / L) and the MCAO group (10.00 卤0.2034ng / L) (P = 6.457 卤0.3743ngL / L) and MCAO group (5.140 卤0.4986ngL / L) respectively (P = 0.0136.657 卤0.3743ngL / L) and MCAO group (5.140 卤0.4986ng / L). P value 0.0011.INF- 纬: there was significant difference between sham operation group (7.177 卤0.6336ng / L) and MCAO group (7.291 卤0.9511 ng / L) and MCAO group (5.882 卤0.5820ng / L) (P = 0.0068.2). The expression of NK- 魏 B applied protein in spleen: there was no significant difference in NF- 魏 B protein expression between sham operation group and DSP-4 MCAO group on the 1st and 2nd day after operation. NF- 魏 B protein expression was significantly decreased in the operative group. Conclusion compared with the sham operation group, the proinflammatory factor and anti-inflammatory factor in the peripheral blood of the rats in the MCAO group were significantly decreased, and the anti-inflammatory factors were significantly increased, while the inflammatory stimulating factors in the peripheral blood of the rats in the DSP-4 MCAO group were significantly higher than those in the sham operation group, while those in the DSP-4 MCAO group were significantly higher than those in the sham operation group. The expression of NF- 魏 B cytokine protein in spleen of MCAO group was significantly lower than that of sham operation group. There was no significant difference between DSP-4 MCAO group and sham operation group.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R743.3

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