本文選題：卒中后免疫抑制 + 藍(lán)斑核��； 參考：《東南大學(xué)》2015年碩士論文

【摘要】：背景：近年來,腦卒中臨床治療得到飛速發(fā)展,腦卒中患者的治愈率和康復(fù)率明顯提高,但是腦卒中治療中仍存在一些懸而未決的臨床難題,其中卒中相關(guān)性感染(stroke-associated infection, SAI)備受人們關(guān)注。感染是急性重癥腦卒中患者最為常見并發(fā)癥,發(fā)生率高達(dá)21～65%,以肺炎和泌尿系感染多見,臨床中往往難于控制,常導(dǎo)致病情急驟惡化,妨礙腦卒中原發(fā)病癥的早期控制和功能康復(fù)。卒中相關(guān)感染被認(rèn)為是病情惡化和死亡的獨立危險因素,給患者及其家庭帶來沉重的負(fù)擔(dān),已成為當(dāng)前神經(jīng)病學(xué)領(lǐng)域重大而亟待解決的臨床難題。目前卒中后免疫抑制機(jī)制主要有四種：原位炎癥反應(yīng)、HPA軸假說、交感神經(jīng)通路假說,我們前期研究已證明卒中后免疫抑制與交感神經(jīng)通路激活具有相關(guān)性,而交感神經(jīng)系統(tǒng)的起源是藍(lán)斑核,應(yīng)激反應(yīng)可激活藍(lán)斑核內(nèi)神經(jīng)元,增強去甲腎上腺素的合成和分泌,以參與喚醒與警戒,而且能增強前額葉的認(rèn)知功能,提高動機(jī)水平,進(jìn)而提高交感神經(jīng)活動。本文主要針對藍(lán)斑核激活與卒中后免疫抑制相關(guān)性進(jìn)行研究。目的：深層次地了解腦卒中后感染的生物學(xué)發(fā)生機(jī)制,將有助于尋找臨床有效且針對性強的治療方法,最終提高腦卒中患者整體預(yù)后。方法：1、分組：MCAO組(線栓法制作大腦中動脈閉塞模型)、DSP-4+MCAO組(使用神經(jīng)毒素DSP-4化學(xué)性破壞腦內(nèi)藍(lán)斑核后制作大腦中動脈閉塞模型)、假手術(shù)組。2、應(yīng)用ELISA方法研究假手術(shù)組、DSP-4+MCAO組、MCAO組血清中炎癥指標(biāo)：IL-10、TNF-α INF-γ的濃度。3、應(yīng)用western-blot方法研究假手術(shù)組、DSP-4+MCAO組、MCAO組脾臟中NF-κB的蛋白表達(dá)4、數(shù)據(jù)采用GraphPad Prism 5、SPSS軟件進(jìn)行統(tǒng)計學(xué)分析,應(yīng)用Excel繪制圖,各指標(biāo)以均數(shù)士標(biāo)準(zhǔn)差(X±S)表示,兩組間的均值比較采用配對t檢驗,多組間資料采用方差分析；所有實驗重復(fù)三次,以P0.05為差異有統(tǒng)計學(xué)意義結(jié)果：1、在外周血中,1L-10濃度：假手術(shù)組(7.726±0.8492ng/L)、DSP-4+MCAO組(8.153±0.8895 ng/L)及 MCAO組(10.00±0.2034ng/L)具有統(tǒng)計學(xué)差異P值=0.0136。TNF-α濃度：假手術(shù)組(6.457±0.3743ng/L)、DSP-4+MCAO 組 (6.433±0.7508ng/L)及MCAO組(5.140±0.4986ng/L)具有統(tǒng)計學(xué)差異P值=0.0011。INF-γ濃度：假手術(shù)組(7.177±0.6336ng/L)、DSP-4+MCAO組(7.291±0.9511 ng/L)及MCAO組(5.882±0.5820ng/L)具有統(tǒng)計學(xué)差異P值=0.0068。2、脾臟中NK-κB運用蛋白表達(dá)：假手術(shù)組及DSP-4+MCAO組術(shù)后第1、2、3天,NF-κB蛋白表達(dá)無明顯差異,MCAO組相對于假手術(shù)組NF-κB蛋白表達(dá)顯著降低。結(jié)論：1、MCAO組大鼠相對于假手術(shù)組外周血中促炎因子明顯降低,抗炎因子明顯升高,出現(xiàn)明顯免疫激活現(xiàn)象；而DSP-4+MCAO組大鼠相對于假手術(shù)組外周血中促炎因子、抗炎因子濃度無顯著變化。2、脾臟中NF-κB細(xì)胞因子蛋白表達(dá)MCAO組相對于假手術(shù)組蛋白表達(dá)明顯降低,DSP-4+MCAO組相對于假手術(shù)組無明顯差異。
[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- 偽 INF- 緯 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 鹵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 鹵0.8492ng / L) and the MCAO group (10.00 鹵0.2034ng / L) (P = 6.457 鹵0.3743ngL / L) and MCAO group (5.140 鹵0.4986ngL / L) respectively (P = 0.0136.657 鹵0.3743ngL / L) and MCAO group (5.140 鹵0.4986ng / L). P value 0.0011.INF- 緯: there was significant difference between sham operation group (7.177 鹵0.6336ng / L) and MCAO group (7.291 鹵0.9511 ng / L) and MCAO group (5.882 鹵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.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R743.3

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