本文選題：旋毛蟲(chóng) + Toll樣受體��； 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：旋毛蟲(chóng)病對(duì)人和動(dòng)物健康、社會(huì)、經(jīng)濟(jì)產(chǎn)生重大影響的食源性人獸共患寄生蟲(chóng)病,該病是由寄生于哺乳動(dòng)物橫紋肌細(xì)胞內(nèi)寄生線蟲(chóng)旋毛蟲(chóng)引起的。在我國(guó)及全世界廣泛分布,給動(dòng)物養(yǎng)殖業(yè)造成嚴(yán)重的經(jīng)濟(jì)損失,對(duì)社會(huì)公共衛(wèi)生產(chǎn)生嚴(yán)重威脅。旋毛蟲(chóng)在長(zhǎng)期進(jìn)化過(guò)程中形成了通過(guò)抑制宿主免疫反應(yīng)而逃避宿主免疫系統(tǒng)攻擊的生存機(jī)制,使其得以順利侵襲與寄生,使宿主處于旋毛蟲(chóng)感染的危險(xiǎn)境地。這種免疫逃避使旋毛蟲(chóng)免疫預(yù)防失效。免疫逃避已成為當(dāng)前旋毛蟲(chóng)有效免疫預(yù)防制劑研制的一個(gè)難以逾越的瓶頸。Toll樣受體(TLRs)在眾多的宿主免疫防御系統(tǒng)扮演了重要角色,TLRs激動(dòng)劑作為抗旋毛蟲(chóng)免疫逃避制劑具有無(wú)法估量的發(fā)展前景。本研究前期通過(guò)灌胃感染旋毛蟲(chóng),利用實(shí)時(shí)熒光定量PCR對(duì)旋毛蟲(chóng)感染的不同階段的TLRs表達(dá)量進(jìn)行檢測(cè),同時(shí)ELISA法檢測(cè)Th1/Th2相關(guān)細(xì)胞因子白細(xì)胞介素-2(IL-2)、白細(xì)胞介素-4(IL-4)、白細(xì)胞介素-10(IL-10)、干擾素-γ(INF-γ)表達(dá)。結(jié)果表明:旋毛蟲(chóng)感染期間,旋毛蟲(chóng)以及其分泌產(chǎn)物能夠不同程度的調(diào)節(jié)宿主的免疫應(yīng)答,在腸期階段TH1反應(yīng)占優(yōu)勢(shì),隨后新生幼蟲(chóng)在骨骼肌期間TH2反應(yīng)占優(yōu)勢(shì)。在感染初期,TLR1、TLR3、TLR4、TLR7和TLR9表達(dá)上調(diào),新生幼蟲(chóng)階段,幾乎所有的TLRs表達(dá)均下調(diào),這表明新生幼蟲(chóng)能夠抑制大多數(shù)TLRs表達(dá)和信號(hào)傳導(dǎo)。對(duì)宿主免疫應(yīng)答具有廣泛的抑制作用。旋毛蟲(chóng)能夠調(diào)節(jié)TLRs的表達(dá)以及其信號(hào)傳導(dǎo)通路。不同感染階段的TLRs表達(dá)對(duì)相關(guān)的信號(hào)傳導(dǎo)通路調(diào)控也不同,說(shuō)明Toll樣受體在旋毛蟲(chóng)感染期間發(fā)揮重要作用,旋毛蟲(chóng)感染能夠誘導(dǎo)條件性Th1、Th2反應(yīng),調(diào)節(jié)T淋巴細(xì)胞和細(xì)胞因子產(chǎn)生,通過(guò)調(diào)節(jié)Toll樣受體表達(dá)來(lái)調(diào)控宿主對(duì)寄生蟲(chóng)的免疫反應(yīng)�；谏鲜鲅芯�,本研究用已報(bào)道的TLRs激動(dòng)劑poly(I:C)、LPS-EB Biotin、TL8-506和OND M362對(duì)小鼠進(jìn)行尾靜脈注射,干預(yù)旋毛蟲(chóng)感染免疫逃避。感染后0、3、6、9、12、15、18、21、28、35天后剖殺小鼠,以人工胃液消化法收集肌幼蟲(chóng)并計(jì)數(shù),計(jì)算減蟲(chóng)率。檢測(cè)TLRs激動(dòng)劑對(duì)旋毛蟲(chóng)感染階段脾TLRs表達(dá)情況,分析血液中Th1/Th2細(xì)胞因子,綜合評(píng)價(jià)4種TLRs激動(dòng)劑對(duì)旋毛蟲(chóng)感染的干預(yù)效果。結(jié)果表明:感染旋毛蟲(chóng)的小鼠注射TLRs激動(dòng)劑后,TLRs激動(dòng)劑能夠激活TLRs,在通過(guò)激動(dòng)劑激活后Th1相關(guān)的細(xì)胞因子IL-2、IFN-γ水平升高,而Th2相關(guān)的細(xì)胞因子IL-4、IL-10降低,在感染的35d剖殺小鼠測(cè)旋毛蟲(chóng)的數(shù)量,計(jì)算減蟲(chóng)率,注射了TLRs激動(dòng)劑后,肌幼蟲(chóng)的數(shù)量均有所下降,說(shuō)明poly(I:C)、LPS-EB Biotin、TL8-506和OND M362均能夠干預(yù)旋毛蟲(chóng)的感染,其中TLR3激動(dòng)劑poly(I:C)的小鼠減蟲(chóng)率達(dá)到最高,效果最佳。本實(shí)驗(yàn)綜合評(píng)價(jià)4種TLRs激動(dòng)劑對(duì)旋毛蟲(chóng)感染的干預(yù)效果,篩選出TLR3激動(dòng)劑poly(I:C)阻礙旋毛蟲(chóng)免疫逃避的最佳TLRs激動(dòng)劑,用于旋毛蟲(chóng)免疫逃避干預(yù)治療,為T(mén)LRs激動(dòng)劑應(yīng)用于旋毛病的防控奠定基礎(chǔ)。本研究不僅對(duì)動(dòng)物和人旋毛蟲(chóng)病防治疫苗研發(fā)意義重大,對(duì)其他寄生蟲(chóng)疫苗的研發(fā)將有不可估量的推動(dòng)作用。
[Abstract]:Trichinosis has a great influence on human and animal health, society and economy. It is caused by the parasitic parasitic Trichinella parasitized in the mammalian rhabdomyid cells. It is widely distributed in China and the world, causing severe economic losses to the animal breeding industry and serious social public health. In the course of long-term evolution, Trichinella spiralis has formed a survival mechanism by inhibiting host immune response and escaping the host immune system attack, making it successful in invasion and parasitism, causing the host to be in the danger of Trichinella infection. This immune escape makes Trichinella Trichinella immune prevention failure. Immune evasion has become a current Trichinella. An insurmountable bottleneck.Toll like receptor (TLRs) has played an important role in many host immune defense systems. The TLRs agonist as an anti Trichinella immune escape agent has an immeasurable prospect. In this study, Trichinella spiralis was infected by gavage of Trichinella spiralis and real time fluorescence quantitative PCR was used for Trichinella spiralis TLRs expression at different stages of infection was detected, while ELISA assay was used to detect interleukin -2 (IL-2), interleukin -4 (IL-4), interleukin -10 (IL-10), and interferon - gamma (INF- gamma). The results showed that Trichinella spiralis and its secretory products could regulate the host in varying degrees during the period of Trichinella infection. The immune response, TH1 reaction predominant during the intestinal stage, and then the TH2 reaction of the newborn larvae during the skeletal muscle. In the early stage of infection, the expression of TLR1, TLR3, TLR4, TLR7 and TLR9 is up regulated, and almost all TLRs expressions are down regulated in the newborn larvae stage, which indicates that the newborn larvae can inhibit most TLRs expression and signal transduction. The answer has extensive inhibition. Trichinella can regulate the expression of TLRs and its signal transduction pathway. The regulation of TLRs expression in different stages of infection is also different, indicating that Toll like receptors play an important role during Trichinella infection. Trichinella infection can induce conditioned Th1, Th2 reaction, and T lymphatic regulation. Cells and cytokines produced by regulating the expression of Toll like receptors to regulate the host's immune response to parasites. Based on the above study, the present study used the reported TLRs agonists, poly (I:C), LPS-EB Biotin, TL8-506 and OND M362 to injecting the tail vein in mice to interfere with the immune evasion of the worm infection. The 0,3,6,9,12,15,18,21,28,35 days after infection. The muscle larvae were collected and counted by artificial gastric juice digestion and the rate of worm reduction was counted. The expression of TLRs agonists on the spleen TLRs expression in the stage of Trichinella Trichinella infection, the analysis of Th1/Th2 cytokine in the blood and the intervention effect of 4 TLRs agonists on Trichinella Trichinella infection were evaluated. The results showed that the mice infected with Trichinella Trichinella were injected with TLRs agonist. After that, TLRs activator activates TLRs and increases the level of Th1 related cytokines IL-2 and IFN- gamma after activation of the agonist, while Th2 related cytokines IL-4 and IL-10 decrease. The number of Trichinella spiralis in infected 35d Caesarean mice is measured and the rate of worm reduction is calculated. After the TLRs agonist is injected, the number of muscle larvae decreases, indicating poly (I:C). B Biotin, TL8-506 and OND M362 can all interfere with Trichinella Trichinella infection, of which the TLR3 agonist poly (I:C) has the highest worm reduction rate and the best effect. This experiment comprehensively evaluated the effect of 4 TLRs agonists on Trichinella Trichinella infection, and screened the best agonist for TLR3 agonist poly (I:C) immune escape from Trichinella Trichinella, used in spin hair. Insect immune avoidance intervention is the basis for the application of TLRs agonists to the prevention and control of circumflex disease. This study is not only of great significance to the research and development of animal and human Trichinella vaccine, but also has an inestimable role in the research and development of other parasitic vaccines.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：S852.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 陳曉英;夏晨陽(yáng);藍(lán)嵐;王燕軍;馬金英;;拉林公路沿線藏豬旋毛蟲(chóng)病血清抗原調(diào)查[J];養(yǎng)豬;2015年05期

2 扎西措姆;金峰;孫萍;;西藏拉薩市旋毛蟲(chóng)病4例報(bào)告[J];中國(guó)寄生蟲(chóng)學(xué)與寄生蟲(chóng)病雜志;2015年04期

3 歐陽(yáng)兆克;郭傳坤;;中國(guó)旋毛蟲(chóng)病流行病學(xué)和血清學(xué)研究概況[J];中國(guó)熱帶醫(yī)學(xué);2015年04期

4 馬思慧;楊歡;吳天成;崔煥忠;張輝;李雨萌;洪盼;鄭鑫;;Toll樣受體信號(hào)傳導(dǎo)通路的研究進(jìn)展[J];中國(guó)畜牧獸醫(yī);2014年08期

5 高明;敖越;欒新紅;曹中贊;;Toll樣受體信號(hào)傳導(dǎo)通路及其免疫調(diào)節(jié)作用的研究進(jìn)展[J];中國(guó)預(yù)防獸醫(yī)學(xué)報(bào);2014年04期

6 王春泉;吳方偉;王興榮;許海兵;李二;龍貴平;李樹(shù)春;白美玲;黃艷;魏忠富;;云南省瀾滄縣一起旋毛蟲(chóng)病暴發(fā)的調(diào)查[J];中國(guó)熱帶醫(yī)學(xué);2013年11期

7 王海英;;旋毛蟲(chóng)病的危害與防治[J];中國(guó)畜禽種業(yè);2013年09期

8 于莉莉;韓代書(shū);;Toll樣受體(TLR)介導(dǎo)的天然免疫間的相互調(diào)節(jié)[J];中國(guó)組織化學(xué)與細(xì)胞化學(xué)雜志;2013年01期

9 鄭德福;肖寧;馮萍;許光榮;歐陽(yáng)清;廖琳;葉萍;陳漪瀾;;1964-2011年中國(guó)大陸人體旋毛蟲(chóng)病流行分析[J];寄生蟲(chóng)病與感染性疾病;2011年03期

10 薛劍;肖樹(shù)華;徐莉莉;張永年;強(qiáng)慧琴;;三苯雙脒和阿苯達(dá)唑治療感染旋毛蟲(chóng)小鼠的療效觀察[J];中國(guó)寄生蟲(chóng)學(xué)與寄生蟲(chóng)病雜志;2010年01期

，

本文編號(hào)：1927531