本文選題：AIF-1 + 日本血吸蟲��； 參考：《華中科技大學(xué)》2011年博士論文

【摘要】：AIF-1，即同種異體移植物炎癥因子-1（allograft inflammatory factor-1），是Utans最先于1995年在大鼠和人異體移植心臟組織中發(fā)現(xiàn)的一種蛋白質(zhì)。隨后的研究發(fā)現(xiàn)AIF-1存在于從紅海鯛、鯉魚和海綿等低等動物低到鼠、豬、牛、人等高等哺乳動物中，且種屬間高度保守。AIF-1是一種早期炎癥因子，在多種與炎癥反應(yīng)相關(guān)的病變中表達(dá)升高，具有非常復(fù)雜、廣泛而重要的生物學(xué)功能。 AIF-1在多種人體自身免疫性疾病、器官移植和實驗性免疫性疾病等組織中過表達(dá)。有人發(fā)現(xiàn)AIF-1的過表達(dá)可以促進(jìn)免疫反應(yīng)由Th1型向Th2型傾斜；另有人發(fā)現(xiàn)AIF-1轉(zhuǎn)基因小鼠的腸炎病變較未轉(zhuǎn)基因小鼠的病變輕，并認(rèn)為這是由于高表達(dá)的AIF-1反饋性抑制Th1型的免疫反應(yīng)所致�，F(xiàn)有研究表明，AIF-1通過與巨噬細(xì)胞、T淋巴細(xì)胞、內(nèi)皮細(xì)胞和TNF-α, IFN-γ, TGF-β等相互影響、相互作用，并通過影響機(jī)體的免疫調(diào)節(jié)系統(tǒng)而發(fā)揮其重要功能。 血吸蟲感染是一個很復(fù)雜的免疫反應(yīng)性炎癥過程，由其導(dǎo)致的肝纖維化、肝硬化嚴(yán)重威脅人類健康和經(jīng)濟(jì)發(fā)展。我們推測，與其他免疫炎癥性病變一樣，感染血吸蟲的宿主的肝、脾等組織中AIF-1表達(dá)增強(qiáng)，而且如果用AIF-1純化物干預(yù)感染小鼠，還可對疾病的進(jìn)程產(chǎn)生明顯影響。因此，我們設(shè)計、實施本課題，并初步證實了我們的設(shè)想。本實驗分二部分： 第一部分：首次證實感染血吸蟲的BALB/c小鼠肝組織有不同程度的AIF-1過表達(dá)，以急性期最強(qiáng)，隨后逐漸下降。ELISA檢測受SEA刺激72小時的脾淋巴細(xì)胞培養(yǎng)上清液中AIF-1的濃度，發(fā)現(xiàn)各感染組均明顯低于正常對照小鼠；同時檢測TNF-α和TGF-β的表達(dá)，發(fā)現(xiàn)這3種細(xì)胞因子的表達(dá)變化有一定的量變關(guān)系。這些結(jié)果提示我們，AIF-1是一種早期炎癥因子，與TNF-α和TGF-β等細(xì)胞因子相互影響，在血吸蟲肝病發(fā)生發(fā)展進(jìn)程中發(fā)揮重要作用。 第二部分：AIF-1純化物干預(yù)血吸蟲感染小鼠，并設(shè)立對照組，發(fā)現(xiàn)AIF-1干預(yù)組在感染后5周時肝細(xì)胞損害稍加重，感染后8周肝組織壞死和纖維化均較對照組減輕，以14周時差異最明顯；Western blot，RT-PCR和ELISA檢測發(fā)現(xiàn)干預(yù)組AIF-1表達(dá)隨感染進(jìn)展而逐漸升高；這表明AIF-1干預(yù)導(dǎo)致血吸蟲慢性感染期小鼠體內(nèi)有效的AIF-1濃度增加，且對肝臟具有保護(hù)作用，說明AIF-1純化物能有效預(yù)防和治療慢性血吸蟲肝病。 如何選擇更有效的干預(yù)時間和劑量，是我們下一步要研究的課題。除此以外，由于各種原因?qū)е碌睦w維化發(fā)生的細(xì)胞、分子機(jī)制相似，深入研究AIF-1抗血吸蟲病肝纖維化作用的分子機(jī)理，可為有效防治其他類似的纖維化病變（如系統(tǒng)性硬化癥、類風(fēng)濕性關(guān)節(jié)炎等）提供理論依據(jù)。 綜上所述，本研究首次證實： 1.日本血吸蟲感染所致BALB/c小鼠肝病組織過表達(dá)AIF-1，以感染急性期最強(qiáng)，后逐漸下降。 2. AIF-1是一種早期炎癥因子，與TNF-α和TGF-β等細(xì)胞因子緊密聯(lián)系并相互作用，在血吸蟲肝病的發(fā)生發(fā)展中發(fā)揮重要的作用。 3. AIF-1純化物干預(yù)導(dǎo)致血吸蟲慢性感染期小鼠體內(nèi)有效AIF-1濃度增加，而其肝組織壞死和纖維化反而明顯減輕。 4. AIF-1純化物干預(yù)能有效預(yù)防和治療慢性血吸蟲肝病。
[Abstract]:It was found in the rat , pig , cattle , human and other high mammals , and highly conserved among the species in the low - grade mammals , such as red sea bream , carp and sponge , and increased in various diseases related to inflammatory response , which had a very complex , broad and important biological function .

It has been found that the overexpression of protein - 1 can promote the immune response from Th1 type to Th2 type .
In addition , it was found that the disease of transgenic mice was less than that of non - transgenic mice , and it was considered to be a result of the high expression of the anti - feed inhibition of Th1 type immune response . The existing study showed that the interaction of the protein with macrophages , T lymphocytes , endothelial cells and TNF - 偽 , IFN - 緯 , TGF - 尾 , and the like , and played an important function by affecting the immune regulation system of the organism .

Schistosoma japonicum infection is a very complicated process of immune response inflammation caused by hepatic fibrosis and cirrhosis , which is a serious threat to human health and economic development .

In the first part , the BALB / c mouse liver tissues infected with Schistosoma japonicum were first confirmed to be overexpressed in different degrees , the strongest in the acute phase and then gradually decreased .
At the same time , the expression of TNF - 偽 and TGF - 尾 was detected , and it was found that the expression changes of these three cytokines have a certain amount . These results suggest that the expression of TNF - 偽 and TGF - 尾 is a kind of early inflammatory factor , which interacts with cytokines such as TNF - 偽 and TGF - 尾 , and plays an important role in the development of liver disease of Schistosoma japonicum .

In the second part , the mice infected with Schistosoma japonicum were infected with the purified protein , and the control group was established . It was found that the hepatocyte injury was slightly increased at 5 weeks after infection , and the necrosis and fibrosis of the liver tissues in 8 weeks after infection were less than those of the control group , and the difference was the most obvious at 14 weeks .
Western blot , RT - PCR and ELISA were used to detect the expression of protein in the intervention group and gradually increase with the progression of infection .
These results suggest that the effective anti - inflammatory activity in the mice infected with Schistosoma japonicum is increased and the protective effect on the liver is indicated , and it is indicated that the purified product can effectively prevent and treat the chronic schistosomiasis liver disease .

How to select more effective intervention time and dosage is the subject of our next step to study . In addition , the molecular mechanism similar to the cell and molecular mechanism caused by various causes is similar , so the molecular mechanism of anti - schistosomiasis liver fibrosis is deeply researched , which can provide theoretical basis for the effective prevention and treatment of other similar fibrotic diseases ( such as systemic sclerosis , rheumatoid arthritis , etc . ) .

In summary , the present study confirms the first time :

1 . The liver disease of BALB / c mice caused by Schistosoma japonicum infection has been overexpressed in BALB / c mice , which is the strongest in the acute phase of infection , and then gradually decreases .

2 . It is an early inflammatory factor that closely links and interacts with cytokines such as TNF - 偽 and TGF - 尾 and plays an important role in the development of liver disease of Schistosoma japonicum .

3 . There was a significant increase in the effective amount of protein - 1 in the body of mice with chronic infection of Schistosoma japonicum , but the necrosis and fibrosis of liver tissue were obviously reduced .

4 . Treatment of chronic schistosomiasis liver disease can be effectively prevented and treated by the intervention of purified protein .

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R383.24

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相關(guān)期刊論文 前2條

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