本文選題：胸腺基質(zhì)淋巴生成素 + 胸腺肽　； 參考：《復(fù)旦大學(xué)》2008年碩士論文

【摘要】： 目的近20年來(lái),包括哮喘、過(guò)敏性鼻炎、特應(yīng)性皮炎和食物過(guò)敏在內(nèi)的過(guò)敏性疾病在經(jīng)濟(jì)發(fā)達(dá)國(guó)家的發(fā)病率逐年升高。在一些西方發(fā)達(dá)國(guó)家,哮喘的發(fā)病率高達(dá)29%。哮喘是兒童時(shí)期最常見(jiàn)的慢性疾病之一,自1980年以來(lái),我國(guó)兒童哮喘的發(fā)病率增加了近1倍。研究證實(shí)從特應(yīng)性皮炎、食物過(guò)敏、過(guò)敏性鼻炎至哮喘的“過(guò)敏歷程(Allergy marches)”,提示可能存在共同的始動(dòng)因素。目前,過(guò)敏性疾病的發(fā)病機(jī)制仍不明確,治療方法也沒(méi)有新的突破。普遍認(rèn)為過(guò)敏性炎癥反應(yīng)是一系列復(fù)雜的免疫級(jí)聯(lián)反應(yīng),表現(xiàn)為Th1/Th2平衡破壞向Th2傾斜,分泌Th2型細(xì)胞因子(如:IL-4、5、13),這些細(xì)胞因子又進(jìn)一步觸發(fā)IgE合成、嗜酸性粒細(xì)胞增多及粘液分泌。多數(shù)研究集中在外周免疫器官和免疫細(xì)胞上,對(duì)中樞性免疫器官——胸腺,在過(guò)敏性疾病發(fā)病機(jī)制中的作用知之甚少。最新的研究發(fā)現(xiàn),胸腺基質(zhì)淋巴生成素(Thymic stromal lymphopoietin,TSLP)在外周能激活DC產(chǎn)生Th2應(yīng)答優(yōu)勢(shì)的炎癥反應(yīng),在胸腺能誘導(dǎo)自身反應(yīng)性T細(xì)胞成為調(diào)節(jié)性T細(xì)胞,從而發(fā)揮控制炎癥反應(yīng)的作用,提示TSLP可能是過(guò)敏性炎癥反應(yīng)的一個(gè)重要促發(fā)因素,胸腺可能在過(guò)敏性疾病的發(fā)病機(jī)制中起重要作用。胸腺肽作為一種免疫調(diào)節(jié)劑,在臨床運(yùn)用多年,對(duì)常規(guī)治療難以控制的哮喘和特應(yīng)性皮炎有一定的治療效果。胸腺肽是一種胸腺組織上皮細(xì)胞分泌的多肽激素,推測(cè)其可能通過(guò)調(diào)節(jié)胸腺功能間接影響過(guò)敏性疾病的發(fā)展。因此,本研究通過(guò)OVA致敏建立小鼠哮喘模型,探討TSLP、胸腺在過(guò)敏性疾病發(fā)病機(jī)制中的作用,同時(shí)用胸腺肽進(jìn)行干預(yù),研究胸腺肽干預(yù)致敏的作用和可能機(jī)制。 方法 1、采用OVA腹腔注射和超聲霧化吸入建立BALB/c小鼠哮喘模型; 2、通過(guò)血清總IgE水平和肺組織病理切片來(lái)評(píng)價(jià)模型; 3、用Real-time PCR檢測(cè)OVA致敏和胸腺肽干預(yù)的不同情況下,小鼠胸腺、肺組織TSLP、Foxp3表達(dá)的變化以及肺組織IFN-γ、IL-4表達(dá)的變化,IFN-γ/IL-4比值的變化;并通過(guò)血清總IgE水平和肺組織病理切片來(lái)評(píng)價(jià)胸腺肽干預(yù)下致敏小鼠的過(guò)敏狀態(tài)。 結(jié)果 1、血清總IgE濃度比較:致敏組與對(duì)照組相比,血清總IgE濃度增加,差異有顯著統(tǒng)計(jì)學(xué)意義(P＜0.05);OVA+胸腺肽組與致敏組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05);單獨(dú)胸腺肽干預(yù)組與對(duì)照組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。 2、肺組織病理切片比較(HE染色):致敏組肺組織病理切片示氣道壁明顯增厚,黏膜下及管壁周圍有較多炎性細(xì)胞浸潤(rùn)。對(duì)照組氣道炎癥反應(yīng)輕,上皮增厚不明顯,氣道周圍炎性細(xì)胞浸潤(rùn)少,肺泡壁結(jié)構(gòu)相對(duì)完整。OVA+胸腺肽組與致敏組相比氣道炎癥反應(yīng)較輕,管壁旁少量炎性細(xì)胞浸潤(rùn),管壁無(wú)明顯增厚。 3、致敏對(duì)小鼠胸腺、肺組織TSLP和Foxp3 mRNA表達(dá)的影響:致敏組小鼠胸腺TSLP mRNA表達(dá)高于對(duì)照組,差異具有非常顯著的統(tǒng)計(jì)學(xué)意義(P＜0.01);胸腺Foxp3 mRNA表達(dá)低于對(duì)照組,差異具有顯著統(tǒng)計(jì)學(xué)意義(P＜0.05)。致敏組肺組織TSLP mRNA表達(dá)同樣高于對(duì)照組,差異具有顯著統(tǒng)計(jì)學(xué)意義(P＜0.05);肺組織Foxp3的表達(dá)與對(duì)照組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。 4、胸腺肽干預(yù)對(duì)致敏小鼠胸腺、肺組織TSLP和Foxp3 mRNA表達(dá)的影響:與致敏組相比,OVA+胸腺肽干預(yù)組胸腺TSLP mRNA的表達(dá)明顯減少,差異具有非常顯著的統(tǒng)計(jì)學(xué)意義(P＜0.01);胸腺Foxp3 mRNA的表達(dá)與致敏組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。OVA+胸腺肽干預(yù)組小鼠肺組織TSLP、Foxp3mRNA的表達(dá)與致敏組比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。 5、單獨(dú)胸腺肽干預(yù)對(duì)小鼠胸腺、肺組織TSLP和Foxp3 mRNA表達(dá)的影響:單獨(dú)胸腺肽干預(yù)組胸腺、肺組織TSLP的表達(dá)與對(duì)照組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。單獨(dú)胸腺肽干預(yù)組胸腺Foxp3 mRNA表達(dá)低于對(duì)照組,差異具有非常顯著的統(tǒng)計(jì)學(xué)意義(P＜0.01);而肺組織Foxp3的表達(dá)高于對(duì)照組,差異具有顯著的統(tǒng)計(jì)學(xué)意義(P＜0.05)。 6、OVA致敏和胸腺肽干預(yù)的不同情況下,小鼠肺組織IL-4、IFN-γmRNA表達(dá)的變化:致敏組肺組織IL-4 mRNA的表達(dá)與對(duì)照組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05);IFN-γmRNA的表達(dá)低于對(duì)照組,差異具有非常顯著的統(tǒng)計(jì)學(xué)意義(P＜0.01);兩組IFN-γ/IL-4比值比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。OVA+胸腺肽干預(yù)組肺組織IL-4、IFN-γmRNA表達(dá)與致敏組相比,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05),兩組IFN-γ/IL-4比值比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。單獨(dú)胸腺肽干預(yù)組肺組織IL-4、IFN-γmRNA表達(dá)與對(duì)照組相比,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05),兩組IFN-γ/IL-4比值比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。 結(jié)論 1、OVA致敏能同時(shí)上調(diào)胸腺和肺TSLP的水平,提示致敏本身能影響到中樞性免疫器官——胸腺。 2、OVA致敏能使胸腺內(nèi)TSLP誘導(dǎo)的Tr分化下調(diào),提示胸腺功能的改變可能與過(guò)敏性疾病的發(fā)生有關(guān)。 3、胸腺肽干預(yù)致敏可下調(diào)胸腺TSLP表達(dá),提示胸腺肽治療過(guò)敏的機(jī)制至少部分是通過(guò)胸腺發(fā)揮作用。
[Abstract]:In recent 20 years , the incidence of allergic diseases , including asthma , allergic rhinitis , atopic dermatitis and food allergy , has increased year by year . In some western developed countries , the incidence of asthma is 29 % .


method


1 . BALB / c mice model was established by intraperitoneal injection of OVA and ultrasonic atomization inhalation .


2 . The model was evaluated by serum total IgE level and pathological section of lung tissue ;


3 . The changes of the expression of IFN - 緯 , IL - 4 and IFN - 緯 / IL - 4 in the thymus , lung tissues , TSLP , Foxp3 and IFN - 緯 / IL - 4 were detected by Real - time PCR .


Results


1 . Compared with the control group , the serum total IgE concentration in the sensitized group was significantly higher than that in the control group ( P < 0.05 ) , and the difference was not statistically significant ( P > 0.05 ) .


2 . Comparison of pathological sections of lung tissues ( HE staining ) : The pathological sections of lung tissues in the sensitized group showed obvious thickening of the airway wall , and there were more inflammatory cell infiltration around the mucous membrane and around the wall .


3 . The effect of sensitization on the expression of TSLP and Foxp3 mRNA in the thymus and lung tissues of mice was significantly higher than that in the control group ( P < 0 . 05 ) . The expression of TSLP mRNA in the lung tissues of the sensitized group was significantly higher than that of the control group ( P < 0 . 05 ) .


4 . The effects of thymosin on the expression of TSLP and Foxp3 mRNA in thymus and lung tissues of sensitized mice showed that the expression of TSLP mRNA in the thymus of OVA + thymosin group was significantly decreased compared with that in the sensitized group ( P & lt ; 0.01 ) . The expression of Foxp3 mRNA was not statistically significant ( P > 0.05 ) . The expression of Foxp3 mRNA was not statistically significant ( P > 0.05 ) .


5 . The effect of single thymosin intervention on the expression of TSLP and Foxp3 mRNA in thymus and lung tissues of mice was significantly higher than that in the control group ( P > 0.05 ) .


Compared with the control group , the expression of IL - 4 and IFN - 緯 mRNA in the lung of the sensitized group was significantly higher than that in the control group ( P > 0.05 ) .


Conclusion


1 . OVA sensitization can increase the level of thymus and lung TSLP at the same time , suggesting that sensitization can affect the central immune organs _ thymus .


2 . OVA sensitization can downregulate Tr differentiation induced by TSLP in thymus , suggesting that changes in thymus function may be related to the occurrence of allergic diseases .


3 . The effect of thymosin on the expression of TSLP in thymus can be downregulated . It is suggested that the mechanism of thymosin treatment is at least partly mediated by thymus .
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R725.6;R392

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