HO-1/CO通过调控TLR4/NF-κB修复胆汁淤积肝损伤肠屏障破坏的研究
发布时间：2021-11-13 14:06
胆汁淤积性肝病由肝细胞和胆管上皮细胞损伤及胆管梗阻导致。胆汁淤积时,细胞外基质合成增加且广泛沉积在肝窦周间隙,肝内胶原纤维异常增生而导致肝纤维化,甚至发展为肝硬化。肝纤维化及肝硬化患者常合并肠道屏障功能障碍,肠道通透性改变;同时肠道微生态改变、细菌和内毒素经门静脉入血,继而激活全身炎症反应,引起多个器官功能障碍。内毒素诱导的全身炎性细胞因子增加和氧化应激又加重肠道和肝损伤,进一步促进细菌移位和内毒素血症。因此保护肠屏障对于阻止肝病进展及预防并发症至关重要。胆汁淤积性肝纤维化时,肠道胆汁酸缺如或减少可导致细菌在肠道内过度生长和菌群结构改变。一些致病性、促炎性微生物,如:紫单胞菌科和肠杆菌科过度生长,肠道通透性增加,脂多糖（lipopolysaccharide,LPS）和细菌移位引起炎症反应,进一步加重肠屏障损害。肠黏膜屏障作为保护机体的第一道防线,可以抵抗肠腔中细菌、食物抗原、毒素等外源性物质的损伤,其中以机械屏障最为重要,其结构基础为完整的肠上皮细胞及之间的紧密连接（tight junction,TJ）。血红素在血红素氧合酶-1（Heme Oxygenase-1,HO-1）的作用下可生...
【文章来源】：大连医科大学辽宁省
【文章页数】：128 页
【学位级别】：博士
【部分图文】：
Caco-2细胞模型培养示意图
Caco-2 细胞单层模型 A：形态学表现：镜下观察 Caco-2 细胞生长形成完整致密的细胞（×100）；B：TEER 检测结果。同浓度 LPS 对 Caco-2 单层细胞 TEER 及紧密连接蛋白的影响在本实验中，我们分别检测了不同浓度的 LPS 对 Caco-2 单层细胞 TEER 的作同时观察了不同浓度 LPS 对肠上皮紧密连接蛋白（ZO-1、occludin 及 claudinmRNA 及蛋白的影响。结果显示和对照组相比，100μg/ml 及 10μg/ml 的 LPS后可以显著降低 Caco-2 单层细胞 TEER 值（图 3A）。同时 qPCR 及 Western blot
图 3 LPS 刺激对 Caco-2 单层细胞 TEER 及紧密连接蛋白的影响。A：TEER 变化；B：不同浓度 LPS 刺激对 claudin-1、occludin 和 ZO-1 mRNA 表达的影响；C：Western blot 方法检测claudin-1、occludin 和 ZO-1 表达；D：经β-actin 标化后，紧密连接蛋白的相对表达量。与对
【参考文献】：
期刊论文
[1]Fatty liver diseases,bile acids,and FXR[J]. Yan Zhu,Hongxia Liu,Min Zhang,Grace L.Guo. Acta Pharmaceutica Sinica B. 2016(05)
[2]Intestinal barrier dysfunction in cirrhosis: Current concepts in pathophysiology and clinical implications[J]. Georgios I Tsiaoussis,Stelios F Assimakopoulos,Athanassios C Tsamandas,Christos K Triantos,Konstantinos C Thomopoulos. World Journal of Hepatology. 2015(17)
[3]Microbiota and the gut-liver axis:Bacterial translocation,inflammation and infection in cirrhosis[J]. Valerio Giannelli,Vincenza Di Gregorio,Valerio Iebba,Michela Giusto,Serena Schippa,Manuela Merli,Ulrich Thalheimer. World Journal of Gastroenterology. 2014(45)
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本文编号：3493156
【文章来源】：大连医科大学辽宁省
【文章页数】：128 页
【学位级别】：博士
【部分图文】：
Caco-2细胞模型培养示意图
Caco-2 细胞单层模型 A：形态学表现：镜下观察 Caco-2 细胞生长形成完整致密的细胞（×100）；B：TEER 检测结果。同浓度 LPS 对 Caco-2 单层细胞 TEER 及紧密连接蛋白的影响在本实验中，我们分别检测了不同浓度的 LPS 对 Caco-2 单层细胞 TEER 的作同时观察了不同浓度 LPS 对肠上皮紧密连接蛋白（ZO-1、occludin 及 claudinmRNA 及蛋白的影响。结果显示和对照组相比，100μg/ml 及 10μg/ml 的 LPS后可以显著降低 Caco-2 单层细胞 TEER 值（图 3A）。同时 qPCR 及 Western blot
图 3 LPS 刺激对 Caco-2 单层细胞 TEER 及紧密连接蛋白的影响。A：TEER 变化；B：不同浓度 LPS 刺激对 claudin-1、occludin 和 ZO-1 mRNA 表达的影响；C：Western blot 方法检测claudin-1、occludin 和 ZO-1 表达；D：经β-actin 标化后，紧密连接蛋白的相对表达量。与对
【参考文献】：
期刊论文
[1]Fatty liver diseases,bile acids,and FXR[J]. Yan Zhu,Hongxia Liu,Min Zhang,Grace L.Guo. Acta Pharmaceutica Sinica B. 2016(05)
[2]Intestinal barrier dysfunction in cirrhosis: Current concepts in pathophysiology and clinical implications[J]. Georgios I Tsiaoussis,Stelios F Assimakopoulos,Athanassios C Tsamandas,Christos K Triantos,Konstantinos C Thomopoulos. World Journal of Hepatology. 2015(17)
[3]Microbiota and the gut-liver axis:Bacterial translocation,inflammation and infection in cirrhosis[J]. Valerio Giannelli,Vincenza Di Gregorio,Valerio Iebba,Michela Giusto,Serena Schippa,Manuela Merli,Ulrich Thalheimer. World Journal of Gastroenterology. 2014(45)
[4]Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury[J]. Clarice Silvia Taemi Origassa,Niels Olsen Saraiva Cmara. World Journal of Hepatology. 2013(10)
[5]Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice[J]. Yu-Kun Zhou,Department of Hepatobiliary Surgery,No.455 Hospital of People’s Liberation Army,Shanghai 200052,China Huan-Long Qin,Ming Zhang,Tong-Yi Shen,Hong-Qi Chen,Yan-Lei Ma,Zhao-Xin Chu,Peng Zhang,Zhi-Hua Liu,Department of Surgery,The Sixth People’s Hospital,Shanghai Jiaotong University,Shanghai 200233,China. World Journal of Gastroenterology. 2012(30)
[6]Enterocytes’tight junctions:From molecules to diseases[J]. Stelios F Assimakopoulos,Ismini Papageorgiou,Aristidis Charonis. World Journal of Gastrointestinal Pathophysiology. 2011(06)
[7]Non-invasive assessment of barrier integrity and function of the human gut[J]. Joep Grootjans,Geertje Thuijls,Froukje Verdam,Joep PM Derikx,Kaatje Lenaerts,Wim A Buurman. World Journal of Gastrointestinal Surgery. 2010(03)
[8]Clinical value of fecal calprotectin in determining disease activity of ulcerative colitis[J]. Jun-Ying Xiang, Qin Ouyang, Guo-Dong Li, Nan-Ping Xiao, Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. World Journal of Gastroenterology. 2008(01)
本文编号：3493156
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