本文選題：囊型包蟲病 + 肝纖維化　； 參考：《新疆大學(xué)》2014年碩士論文

【摘要】：棘球蚴病（Echinococcosis），又稱為包蟲病，是由棘球絳蟲的幼蟲寄生于宿主體內(nèi)導(dǎo)致的一種人畜共患寄生蟲疾病，其中，95%的病例為細(xì)粒棘球絳蟲（Echinococcus granulosus, E.g）感染所致的囊型包蟲病（Cystis Echinococcosis,CE）該病呈全球分布，后果較為嚴(yán)重。microRNA隸屬于非編碼小RNA（smallnoncoding RNAs），長度為18-23個核苷酸，它可以通過mRNA剪切或與靶基因mRNA結(jié)合而干擾其轉(zhuǎn)錄過程來調(diào)控靶基因在蛋白水平的表達(dá)�，F(xiàn)已在哺乳動物鑒定出約1400個miRNA，每個miRNA可以影響數(shù)百個基因的轉(zhuǎn)錄，而每個mRNA也可被多個miRNA調(diào)節(jié)。越來越多的研究顯示，miRNA在肝臟的分化及其形態(tài)和功能維持和包括寄生蟲感染在內(nèi)的肝臟疾病的發(fā)生發(fā)展密切相關(guān)�，F(xiàn)有研究顯示miR-19b在肝星狀細(xì)胞HSC活化進(jìn)程中表達(dá)量下調(diào)，與之相似的是，miR-19b在肝纖維化患者的肝臟組織和肝纖維化的小鼠模型中的表達(dá)下調(diào)；miR-19b過表達(dá)可通過抑制其靶基因TGFβRII的表達(dá)而達(dá)到抑制TGF-β信號通路的效果，進(jìn)而抑制細(xì)胞中α-SMA和膠原蛋白的表達(dá)。探討miR-19b在囊性包蟲病患者肝臟組織中的表達(dá)情況，，對于囊性包蟲病發(fā)病機(jī)制的研究有重要的理論和臨床意義。我們通過QRT-PCR檢測α-SMA、COL1A1、COL3A1、TGFβRII及miR-19b在囊性包蟲病患者肝臟組織中的表達(dá)；并檢測了HCF外源刺激對人肝星狀細(xì)胞LX-2增殖的影響，最后通過脂質(zhì)體2000轉(zhuǎn)染miR-19b及miRNA-NC分析miR-19b對HCF所致LX-2細(xì)胞增殖過程中的調(diào)控。結(jié)果顯示囊性包蟲病患者肝臟組織中，α-SMA、COL1A1、COL3A1和TGFβRII mRNA在病灶近旁部位的表達(dá)量較遠(yuǎn)端組織增加；miR-19b在病灶近旁部位的表達(dá)較遠(yuǎn)端組織的表達(dá)量下降，且miR-19b表達(dá)量與COL1A1的表達(dá)量負(fù)相關(guān)。向體外培養(yǎng)的LX-2細(xì)胞中添加外源HCF發(fā)現(xiàn)，HCF可通過促進(jìn)LX-2細(xì)胞由G0/G1期向S期的轉(zhuǎn)變而促進(jìn)細(xì)胞增殖，與此同時，HCF外源刺激可促進(jìn)α-SMA、COL1A1、COL3A1和TGFβRII mRNA及蛋白水平表達(dá)的增加。miR-19b過表達(dá)可抑制LX-2細(xì)胞的增殖，并通過阻礙TGF-β信號傳遞而達(dá)到降低COL1A1和COL3A1沉積的效果，從而延緩或逆轉(zhuǎn)纖維化的進(jìn)程。因此， miR-19b可能成為囊性包蟲病治療的潛在靶點(diǎn)。
[Abstract]:Echinococcus coensis, also known as echinococcosis, is a zoonotic parasitic disease caused by the larva of Echinococcus granulosus. Among them, 95% of the cases were caused by Echinococcus granulosus (E.g) infection. Cystis Echinococcus coensis (CEE) was a global disease with serious consequences. MicroRNAs belonged to a small, non-coding RNA(smallnoncoding, RNAsN, with a length of 18-23 nucleotides. It can interfere with the transcriptional process of target gene by mRNA splicing or binding with target gene mRNA to regulate the expression of target gene at protein level. About 1400 miRNAs have been identified in mammals, each miRNA can affect the transcription of hundreds of genes, and each mRNA can also be regulated by multiple miRNA. More and more studies have shown that miRNA is closely related to liver differentiation, morphological and functional maintenance, and the occurrence and development of liver diseases including parasitic infection. Current studies have shown that miR-19b expression is down-regulated in the process of HSC activation in hepatic stellate cells. Similarly, the down-regulated expression of miR-19b in liver tissues of patients with liver fibrosis and mouse model of liver fibrosis can inhibit the signal pathway of TGF- 尾 by inhibiting the expression of its target gene TGF 尾 RII. Furthermore, the expression of 偽 -SMA and collagen was inhibited. To investigate the expression of miR-19b in liver tissue of patients with cystic hydatid disease, it is of great theoretical and clinical significance to study the pathogenesis of cystic hydatid disease. The expression of TGF- 尾 RII and miR-19b in liver tissues of patients with cystic hydatid disease was detected by QRT-PCR, and the effect of exogenous stimulation of HCF on LX-2 proliferation of human hepatic stellate cells was detected. Finally, the regulation of miR-19b on the proliferation of LX-2 cells induced by HCF was analyzed by transfection of liposome 2000 into miR-19b and miRNA-NC. The results showed that the expression of 偽 -SMA-COL1A1 and TGF 尾 RII mRNA in liver tissues of patients with cystic hydatid disease was higher than that in distal tissues, and the expression of miR-19b was negatively correlated with the expression of COL1A1. It was found that the addition of exogenous HCF to LX-2 cells in vitro could promote the proliferation of LX-2 cells by promoting the transformation of LX-2 cells from G0/G1 phase to S phase. At the same time, the overexpression of 偽 -SMA-COL1A1 and TGF 尾 RII mRNA and protein could inhibit the proliferation of LX-2 cells and reduce the deposition of COL1A1 and COL3A1 by blocking TGF- 尾 signal transduction. Thus delaying or reversing the process of fibrosis. Therefore, miR-19b may be a potential target for the treatment of cystic hydatid disease.
【學(xué)位授予單位】：新疆大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R532.32

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 陳雪玲,吳向未,彭心宇,張示杰,牛建華,孫紅;PDGF、TNF-α在人肝細(xì)粒棘球蚴囊壁周圍組織的分層表達(dá)[J];現(xiàn)代免疫學(xué);2004年03期

2 溫浩,欒梅香,楊文光,李俊,邱杰;肝包蟲病的標(biāo)準(zhǔn)化分型及臨床意義探討[J];新疆醫(yī)科大學(xué)學(xué)報;2002年02期

3 周曉濤;林仁勇;張亞樓;馬海龍;張雪;盧曉梅;劉輝;許晏;溫浩;呂國棟;劉濤;;泡球蚴囊液對原代培養(yǎng)大鼠肝細(xì)胞增殖影響的初步研究[J];中國病原生物學(xué)雜志;2008年03期

4 吳向未,陳雪玲,彭心宇,張示杰,牛建華,孫紅;Ⅰ、Ⅲ、Ⅳ型膠原在肝包蟲囊腫周圍人體纖維囊壁中的特異性分層表達(dá)[J];中國人獸共患病雜志;2004年10期

5 彭心宇;李建輝;趙瑾;吳向未;張示杰;牛建華;楊宏強(qiáng);孫紅;;肝細(xì)粒棘球蚴周圍纖維囊壁鈣化分布及意義[J];中國人獸共患病學(xué)報;2006年09期

6 印雙紅;陳小林;徐芳潔;張旭勇;吳向未;侯雋;陳雪玲;;小鼠細(xì)粒棘球蚴感染早期對NK細(xì)胞影響的初步研究[J];中國免疫學(xué)雜志;2013年11期

本文編號：1781212