代谢相关性脂肪性肝病异质性的组学分析
发布时间:2021-10-25 14:52
目的:以代谢相关性脂肪性肝病(metabolic associated fatty liver disease,MAFLD)的异质性为研究内容,从饮食摄入的角度切入,探索肝脏代谢稳态变化背后的肝脏功能基因表达改变以及肠道菌群的物种组成和功能代谢通路的变化。研究在脂肪肝(fatty liver disease,FLD)这一相同表型之下,是否存在着多种不同的基因和菌群的变化模式,而这些不同的模式又是分别通过何种致病机制来导致FLD的。充分认识这背后的异质性,可以使我们更加深入地理解MAFLD的病因病机,并在临床实践中,能针对不同异质性的患者亚型,更为精准地去干预肝脏分子靶点和肠道菌群功能代谢,从而实现个体化精准医疗的目标。方法:分别以高脂饲料(high fat diet,HFD)、2%蛋氨酸添加饲料(high-methionine diet)、叶酸缺乏饲料(folate deficient diet,FD diet)构建高脂小鼠、高同型半胱氨酸血症(hyperhomocysteinaemia,HHcy)小鼠、叶酸缺乏小鼠,这三种饮食干预诱导出的模型小鼠均有肝脏脂肪变性。然后取三种不同干预方...
【文章来源】:昆明医科大学云南省
【文章页数】:69 页
【学位级别】:硕士
【部分图文】:
图1.1干预喂养14周时小鼠肝组织油红O染色??A:正常对照组;B:?HFD组;C:?HHcy组;D:?FD组??
首先对从各个样本提取出的总RNA的纯度和完整度等指标进行了检测。采用??Agilent?2100?Bioanalyzer检测RNA的完整性,选取RNA18S和28S亚基出峰完??整、集中程度尚,且RNA完整度值(RNA?integrity?number,R1N)较高的样本??(图1.2),可认为按要求选出的样本RNA完整,没有发生降解,并且纯度和??浓度较高,可以进行后续转录组学测序分析。最终分别保留了正常对照组3个,??HHcy组3个,FD组3个、HFD组4个较高质量样本。??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?
图1.5A)?;?N与HHcy比较,有DEGs884个,其中上??调556个,下调328个(图1.5B)?;?N与FD比较,有DEGsl56丨个,其中上调??782个,下调779个(图1.5C)
【参考文献】:
期刊论文
[1]微生物组数据分析方法与应用[J]. 刘永鑫,秦媛,郭晓璇,白洋. 遗传. 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;. 实用肝脏病杂志. 2018(02)
[4]细胞色素P450家族与非酒精性脂肪肝的关系[J]. 陈裕荷,任红,彭明利. 肝脏. 2017(10)
[5]基因表达谱分析非酒精性脂肪肝中细胞色素P450的作用[J]. 刘玉,成飞,罗玉璇,胡鹏,任红,彭明利. 中华肝脏病杂志. 2017 (04)
[6]精准医学的需求与挑战[J]. 张华,詹启敏. 中国研究型医院. 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)
本文编号:3457629
【文章来源】:昆明医科大学云南省
【文章页数】:69 页
【学位级别】:硕士
【部分图文】:
图1.1干预喂养14周时小鼠肝组织油红O染色??A:正常对照组;B:?HFD组;C:?HHcy组;D:?FD组??
首先对从各个样本提取出的总RNA的纯度和完整度等指标进行了检测。采用??Agilent?2100?Bioanalyzer检测RNA的完整性,选取RNA18S和28S亚基出峰完??整、集中程度尚,且RNA完整度值(RNA?integrity?number,R1N)较高的样本??(图1.2),可认为按要求选出的样本RNA完整,没有发生降解,并且纯度和??浓度较高,可以进行后续转录组学测序分析。最终分别保留了正常对照组3个,??HHcy组3个,FD组3个、HFD组4个较高质量样本。??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?
图1.5A)?;?N与HHcy比较,有DEGs884个,其中上??调556个,下调328个(图1.5B)?;?N与FD比较,有DEGsl56丨个,其中上调??782个,下调779个(图1.5C)
【参考文献】:
期刊论文
[1]微生物组数据分析方法与应用[J]. 刘永鑫,秦媛,郭晓璇,白洋. 遗传. 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;. 实用肝脏病杂志. 2018(02)
[4]细胞色素P450家族与非酒精性脂肪肝的关系[J]. 陈裕荷,任红,彭明利. 肝脏. 2017(10)
[5]基因表达谱分析非酒精性脂肪肝中细胞色素P450的作用[J]. 刘玉,成飞,罗玉璇,胡鹏,任红,彭明利. 中华肝脏病杂志. 2017 (04)
[6]精准医学的需求与挑战[J]. 张华,詹启敏. 中国研究型医院. 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)
本文编号:3457629
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