PPARα/γ信号通路在高脂性脂肪性肝炎发病机制中的作用研究
发布时间:2021-01-14 07:31
目的:研究核受体PPARα/γ信号通路在高脂性脂肪性肝炎发病中的作用及其可能的病理机制,为合理使用作用于PPARα/γ靶标的药物治疗高脂性脂肪性肝炎提供依据。方法:体内试验采用雄性SD大鼠,随机分为溶媒对照组、高脂性脂肪性肝炎模型组、PPARα激动剂非诺贝特20 mg/kg组、PPARγ激动剂罗格列酮4 mg/kg组、非诺贝特+罗格列酮组、PPARα拮抗剂(MK886)1 mg/kg组、PPARγ拮抗剂(GW9662)1 mg/kg组和PPARα/γ拮抗剂组。在用高脂高糖乳剂复制高脂性脂肪性肝炎模型时,同时给予相应的药物处理6周,然后取血液和肝脏,测定血和肝中总胆固醇(TC)、甘油三酯(TG)和游离脂肪酸(FFA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)含量、炎症细胞因子TNF-α、IL-6、IL-8和MCP-1水平,以及血中谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,并计算肝重指数;在光镜下观察肝脏的形态学改变;采用RT-PCR和Western blot方法检测肝组织中过氧化物酶体增殖物激活受体(PPAR)α/γ、固醇调节元件结合蛋白(SREBP)-1c、...
【文章来源】:苏州大学江苏省
【文章页数】:143 页
【学位级别】:博士
【文章目录】:
中文摘要
Abstract
前言
第一部分 PPARα/γ 激动剂和拮抗剂对大鼠高脂性脂肪性肝炎形成的不同影响
材料与方法
实验结果
小结
第二部分 PPARα/γ 激动剂和拮抗剂对高脂性脂肪性肝炎大鼠脂代谢及炎症通路基因表达的影响
材料与方法
实验结果
小结
第三部分 PPARα/γ 激动剂和/或拮抗剂对培养肝细胞脂代谢及炎症通路基因表达的影响
材料与方法
实验结果
小结
第四部分 讨论
结论
创新点
参考文献
攻读博士学位期间发表的文章
攻读博士学位期间立项的课题
附录
附录一 综述
References
附录二 缩写词表
致谢
【参考文献】:
期刊论文
[1]Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome[J]. Adam S Bodzin,Ronald W Busuttil. World Journal of Hepatology. 2015(09)
[2]Non-alcoholic fatty liver disease: The diagnosis and management[J]. Shehab M Abd El-Kader,Eman M Salah El-Den Ashmawy. World Journal of Hepatology. 2015(06)
[3]Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J]. Yoshihisa Takahashi,Keiichiro Sugimoto,Hiroshi Inui,Toshio Fukusato. World Journal of Gastroenterology. 2015(13)
[4]Non-alcoholic fatty liver disease and psoriasis: So far, so near[J]. Giulia Ganzetti,Anna Campanati,Annamaria Offidani. World Journal of Hepatology. 2015(03)
[5]Role of diet on non-alcoholic fatty liver disease: An updated narrative review[J]. Dimitrios Papandreou,Eleni Andreou. World Journal of Hepatology. 2015(03)
[6]Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease[J]. Long-Xin Qiu,Tong Chen. World Journal of Gastroenterology. 2015(04)
[7]Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies[J]. Masayoshi Takeuchi,Jun-ichi Takino,Akiko Sakasai-Sakai,Takanobu Takata,Tadashi Ueda,Mikihiro Tsutsumi,Hideyuki Hyogo,Sho-ichi Yamagishi. World Journal of Hepatology. 2014(12)
[8]GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells[J]. Xiao-Min Xin,Mu-Xiao Zhong,Gong-Li Yang,Yao Peng,Ya-Li Zhang,Wei Zhu. World Journal of Gastroenterology. 2014(42)
[9]Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease[J]. Giuseppe Paradies,Valeria Paradies,Francesca M Ruggiero,Giuseppe Petrosillo. World Journal of Gastroenterology. 2014(39)
[10]Peroxisome proliferator-activated receptors for hypertension[J]. Daisuke Usuda,Tsugiyasu Kanda. World Journal of Cardiology. 2014(08)
本文编号:2976496
【文章来源】:苏州大学江苏省
【文章页数】:143 页
【学位级别】:博士
【文章目录】:
中文摘要
Abstract
前言
第一部分 PPARα/γ 激动剂和拮抗剂对大鼠高脂性脂肪性肝炎形成的不同影响
材料与方法
实验结果
小结
第二部分 PPARα/γ 激动剂和拮抗剂对高脂性脂肪性肝炎大鼠脂代谢及炎症通路基因表达的影响
材料与方法
实验结果
小结
第三部分 PPARα/γ 激动剂和/或拮抗剂对培养肝细胞脂代谢及炎症通路基因表达的影响
材料与方法
实验结果
小结
第四部分 讨论
结论
创新点
参考文献
攻读博士学位期间发表的文章
攻读博士学位期间立项的课题
附录
附录一 综述
References
附录二 缩写词表
致谢
【参考文献】:
期刊论文
[1]Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome[J]. Adam S Bodzin,Ronald W Busuttil. World Journal of Hepatology. 2015(09)
[2]Non-alcoholic fatty liver disease: The diagnosis and management[J]. Shehab M Abd El-Kader,Eman M Salah El-Den Ashmawy. World Journal of Hepatology. 2015(06)
[3]Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J]. Yoshihisa Takahashi,Keiichiro Sugimoto,Hiroshi Inui,Toshio Fukusato. World Journal of Gastroenterology. 2015(13)
[4]Non-alcoholic fatty liver disease and psoriasis: So far, so near[J]. Giulia Ganzetti,Anna Campanati,Annamaria Offidani. World Journal of Hepatology. 2015(03)
[5]Role of diet on non-alcoholic fatty liver disease: An updated narrative review[J]. Dimitrios Papandreou,Eleni Andreou. World Journal of Hepatology. 2015(03)
[6]Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease[J]. Long-Xin Qiu,Tong Chen. World Journal of Gastroenterology. 2015(04)
[7]Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies[J]. Masayoshi Takeuchi,Jun-ichi Takino,Akiko Sakasai-Sakai,Takanobu Takata,Tadashi Ueda,Mikihiro Tsutsumi,Hideyuki Hyogo,Sho-ichi Yamagishi. World Journal of Hepatology. 2014(12)
[8]GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells[J]. Xiao-Min Xin,Mu-Xiao Zhong,Gong-Li Yang,Yao Peng,Ya-Li Zhang,Wei Zhu. World Journal of Gastroenterology. 2014(42)
[9]Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease[J]. Giuseppe Paradies,Valeria Paradies,Francesca M Ruggiero,Giuseppe Petrosillo. World Journal of Gastroenterology. 2014(39)
[10]Peroxisome proliferator-activated receptors for hypertension[J]. Daisuke Usuda,Tsugiyasu Kanda. World Journal of Cardiology. 2014(08)
本文编号:2976496
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