代謝相關(guān)性脂肪性肝病異質(zhì)性的組學(xué)分析
發(fā)布時(shí)間:2021-10-25 14:52
目的:以代謝相關(guān)性脂肪性肝。╩etabolic associated fatty liver disease,MAFLD)的異質(zhì)性為研究?jī)?nèi)容,從飲食攝入的角度切入,探索肝臟代謝穩(wěn)態(tài)變化背后的肝臟功能基因表達(dá)改變以及腸道菌群的物種組成和功能代謝通路的變化。研究在脂肪肝(fatty liver disease,FLD)這一相同表型之下,是否存在著多種不同的基因和菌群的變化模式,而這些不同的模式又是分別通過(guò)何種致病機(jī)制來(lái)導(dǎo)致FLD的。充分認(rèn)識(shí)這背后的異質(zhì)性,可以使我們更加深入地理解MAFLD的病因病機(jī),并在臨床實(shí)踐中,能針對(duì)不同異質(zhì)性的患者亞型,更為精準(zhǔn)地去干預(yù)肝臟分子靶點(diǎn)和腸道菌群功能代謝,從而實(shí)現(xiàn)個(gè)體化精準(zhǔn)醫(yī)療的目標(biāo)。方法:分別以高脂飼料(high fat diet,HFD)、2%蛋氨酸添加飼料(high-methionine diet)、葉酸缺乏飼料(folate deficient diet,FD diet)構(gòu)建高脂小鼠、高同型半胱氨酸血癥(hyperhomocysteinaemia,HHcy)小鼠、葉酸缺乏小鼠,這三種飲食干預(yù)誘導(dǎo)出的模型小鼠均有肝臟脂肪變性。然后取三種不同干預(yù)方...
【文章來(lái)源】:昆明醫(yī)科大學(xué)云南省
【文章頁(yè)數(shù)】:69 頁(yè)
【學(xué)位級(jí)別】:碩士
【部分圖文】:
圖1.1干預(yù)喂養(yǎng)14周時(shí)小鼠肝組織油紅O染色??A:正常對(duì)照組;B:?HFD組;C:?HHcy組;D:?FD組??
首先對(duì)從各個(gè)樣本提取出的總RNA的純度和完整度等指標(biāo)進(jìn)行了檢測(cè)。采用??Agilent?2100?Bioanalyzer檢測(cè)RNA的完整性,選。遥危粒保福雍停玻福觼喕龇逋??整、集中程度尚,且RNA完整度值(RNA?integrity?number,R1N)較高的樣本??(圖1.2),可認(rèn)為按要求選出的樣本RNA完整,沒(méi)有發(fā)生降解,并且純度和??濃度較高,可以進(jìn)行后續(xù)轉(zhuǎn)錄組學(xué)測(cè)序分析。最終分別保留了正常對(duì)照組3個(gè),??HHcy組3個(gè),FD組3個(gè)、HFD組4個(gè)較高質(zhì)量樣本。??TYR19054776?[?1:4?]??(FU】?—??100-?!?I??50-?I?=?—??Q?_?1?I?f?—r?<?^.?‘??I?I?I?I?I?I?—??25?200?1000?4000?[nt]??Overall?Results?for?sample?1?:?TYR19054776??RNAA/ea:?592.8??RNA?Concentration:?270?ng/pl??r^NA?Ratio?[28s?/?18s]:?1.1??RNA?Integrity?Number?(RIN):?9?(a〇2.09)??Result?Ragging?Cotof:?I?1??Result?Ragging?Label:?RIN:9??Fragment?table?for?sample?1?:?TVR19054776??Name?Start?Size?[nt]?End?Size?[nt]?Area?%?of?total?Area??18S?1,631?2,138?1303?220??28S?
圖1.5A)?;?N與HHcy比較,有DEGs884個(gè),其中上??調(diào)556個(gè),下調(diào)328?jìng)(gè)(圖1.5B)?;?N與FD比較,有DEGsl56丨個(gè),其中上調(diào)??782個(gè),下調(diào)779個(gè)(圖1.5C)
【參考文獻(xiàn)】:
期刊論文
[1]微生物組數(shù)據(jù)分析方法與應(yīng)用[J]. 劉永鑫,秦媛,郭曉璇,白洋. 遺傳. 2019(09)
[2]Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity[J]. Carlos J Pirola,Silvia Sookoian. World Journal of Gastroenterology. 2018(15)
[3]非酒精性脂肪性肝病防治指南(2018年更新版)[J]. National Workshop on Fatty Liver and Alcoholic Liver Disease,Chinese Society of Hepatology,Chinese Medical Association;Fatty Liver Expert Committee,Chinese Medical Doctor Association;. 實(shí)用肝臟病雜志. 2018(02)
[4]細(xì)胞色素P450家族與非酒精性脂肪肝的關(guān)系[J]. 陳裕荷,任紅,彭明利. 肝臟. 2017(10)
[5]基因表達(dá)譜分析非酒精性脂肪肝中細(xì)胞色素P450的作用[J]. 劉玉,成飛,羅玉璇,胡鵬,任紅,彭明利. 中華肝臟病雜志. 2017 (04)
[6]精準(zhǔn)醫(yī)學(xué)的需求與挑戰(zhàn)[J]. 張華,詹啟敏. 中國(guó)研究型醫(yī)院. 2015(05)
[7]Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease[J]. Giulia Paolella,Claudia Mandato,Luca Pierri,Marco Poeta,Martina Di Stasi,Pietro Vajro. World Journal of Gastroenterology. 2014(42)
[8]Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis[J]. Yaron Ilan. World Journal of Gastroenterology. 2012(21)
[9]Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J]. Yoshihisa Takahashi,Yurie Soejima,Toshio Fukusato. World Journal of Gastroenterology. 2012(19)
本文編號(hào):3457629
【文章來(lái)源】:昆明醫(yī)科大學(xué)云南省
【文章頁(yè)數(shù)】:69 頁(yè)
【學(xué)位級(jí)別】:碩士
【部分圖文】:
圖1.1干預(yù)喂養(yǎng)14周時(shí)小鼠肝組織油紅O染色??A:正常對(duì)照組;B:?HFD組;C:?HHcy組;D:?FD組??
首先對(duì)從各個(gè)樣本提取出的總RNA的純度和完整度等指標(biāo)進(jìn)行了檢測(cè)。采用??Agilent?2100?Bioanalyzer檢測(cè)RNA的完整性,選。遥危粒保福雍停玻福觼喕龇逋??整、集中程度尚,且RNA完整度值(RNA?integrity?number,R1N)較高的樣本??(圖1.2),可認(rèn)為按要求選出的樣本RNA完整,沒(méi)有發(fā)生降解,并且純度和??濃度較高,可以進(jìn)行后續(xù)轉(zhuǎn)錄組學(xué)測(cè)序分析。最終分別保留了正常對(duì)照組3個(gè),??HHcy組3個(gè),FD組3個(gè)、HFD組4個(gè)較高質(zhì)量樣本。??TYR19054776?[?1:4?]??(FU】?—??100-?!?I??50-?I?=?—??Q?_?1?I?f?—r?<?^.?‘??I?I?I?I?I?I?—??25?200?1000?4000?[nt]??Overall?Results?for?sample?1?:?TYR19054776??RNAA/ea:?592.8??RNA?Concentration:?270?ng/pl??r^NA?Ratio?[28s?/?18s]:?1.1??RNA?Integrity?Number?(RIN):?9?(a〇2.09)??Result?Ragging?Cotof:?I?1??Result?Ragging?Label:?RIN:9??Fragment?table?for?sample?1?:?TVR19054776??Name?Start?Size?[nt]?End?Size?[nt]?Area?%?of?total?Area??18S?1,631?2,138?1303?220??28S?
圖1.5A)?;?N與HHcy比較,有DEGs884個(gè),其中上??調(diào)556個(gè),下調(diào)328?jìng)(gè)(圖1.5B)?;?N與FD比較,有DEGsl56丨個(gè),其中上調(diào)??782個(gè),下調(diào)779個(gè)(圖1.5C)
【參考文獻(xiàn)】:
期刊論文
[1]微生物組數(shù)據(jù)分析方法與應(yīng)用[J]. 劉永鑫,秦媛,郭曉璇,白洋. 遺傳. 2019(09)
[2]Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity[J]. Carlos J Pirola,Silvia Sookoian. World Journal of Gastroenterology. 2018(15)
[3]非酒精性脂肪性肝病防治指南(2018年更新版)[J]. National Workshop on Fatty Liver and Alcoholic Liver Disease,Chinese Society of Hepatology,Chinese Medical Association;Fatty Liver Expert Committee,Chinese Medical Doctor Association;. 實(shí)用肝臟病雜志. 2018(02)
[4]細(xì)胞色素P450家族與非酒精性脂肪肝的關(guān)系[J]. 陳裕荷,任紅,彭明利. 肝臟. 2017(10)
[5]基因表達(dá)譜分析非酒精性脂肪肝中細(xì)胞色素P450的作用[J]. 劉玉,成飛,羅玉璇,胡鵬,任紅,彭明利. 中華肝臟病雜志. 2017 (04)
[6]精準(zhǔn)醫(yī)學(xué)的需求與挑戰(zhàn)[J]. 張華,詹啟敏. 中國(guó)研究型醫(yī)院. 2015(05)
[7]Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease[J]. Giulia Paolella,Claudia Mandato,Luca Pierri,Marco Poeta,Martina Di Stasi,Pietro Vajro. World Journal of Gastroenterology. 2014(42)
[8]Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis[J]. Yaron Ilan. World Journal of Gastroenterology. 2012(21)
[9]Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J]. Yoshihisa Takahashi,Yurie Soejima,Toshio Fukusato. World Journal of Gastroenterology. 2012(19)
本文編號(hào):3457629
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