声明
摘要
符号及缩略语
主要试剂及来源
主要仪器设备
第一部分原发性痛风患者血清尿酸、胰岛素样生长因子-1与甘油三酯水平相关性研究
2高尿酸血症在痛风发病中的地位
3胰岛素样生长因子-1与痛风的关系
4甘油三酯与痛风的关系
5本课题的研究策略及意义
资料和方法
1病例资料来源
2本研究采用的原发性痛风诊断标准
3排除标准
4研究方法
5统计学分析
结果
1病例材料及检测指标的变化特征
2血清尿酸水平与其它指标之间的关系
3血清IGF-1水平与其它指标之间的关系
讨论
1 探讨各项指标之间相关关系的意义
2血清尿酸水平与其它各项指标之间关系的意义
3血清IGg-1水平与其它指标之间关系的意义
4认识到高尿酸血症的临床意义的重要性
5本研究的缺陷或不足之处
6结论
参考文献
第二部分高尿酸诱导甘油三酯代谢紊乱的作用和机制
2高尿酸与甘油三酯之间的关系的研究现状
3影响脂质代谢的相关信号通路
4本研究的策略、目的及意义
材料和方法
3油红O染色
4尿酸测定
5甘油三酯测定
6酮体测定
7免疫组织化学染色
8Real-time RT-PCR检测分析
9Western blot检测分析
10统计学分析
结果
1尿酸诱导脂肪代谢紊乱细胞模型和小鼠动物模型的建立
2尿酸刺激对甘油三酯水平的影响
3尿酸刺激对酮体水平的影响
4尿酸刺激对脂肪代谢酶的影响
5尿酸刺激对细胞内信号通路的影响
讨论
1探讨高尿酸与甘油三酯之间的关系的意义
2高尿酸对甘油三酯变化的影响程度
3高尿酸对甘油三酯变化影响的途径
4高尿酸对甘油三酯变化影响的细胞信号通路
5结论
参考文献
第三部分IGF-1通过IRS1／PI3K信号通路改善高尿酸诱导的脂质代谢紊乱
前言
3IGF-1通过IRS1／PI3K信号通路的生物学作用
4本研究的策略、目的及意义
材料和方法
2IGF-1对高尿酸诱导甘油三酯水平异常的干预效应检测分析
3小鼠血清尿酸水平检测
4IGF-1对高尿酸诱导酮体水平异常的效应检测分析
5IGF-1对高尿酸所致脂肪代谢酶水平变化的干预效应检测分析
6IGF-1对高尿酸诱导脂肪代谢调控和转录因子表达水平异常的干预效应检测分析
7IGF-1在高尿酸致IRS1／PI3K／Akt信号通路异常中作用检测分析
8统计学分析
结果
1IGF-1抑制高尿酸诱发的甘油三酯水平升高
2IGF-1改善高尿酸诱发的酮体水平降低
3IGF-1改善高尿酸对脂肪代谢酶表达的影响
4IGF-1改善高尿酸对对脂质代谢转录因子表达的影响
5IGF-1减轻高尿酸对IRS1／PI3K／Akt信号通路的干扰作用
讨论
1本研究的发现及其意义
2IGF-1通过IRS1／PI3K／Akt信号通路在脂质代谢中的作用地位
3氧化应激机制与甘油三酯代谢紊乱之间的关系
4高尿酸对脂肪酸氧化代谢过程的抑制作用
5结论
参考文献
综述
Part Ⅰ Correlation of serum uric acid and insulin-like growth factor-1 with triglyceride levels in gout patients
Inctroduction
1 Current situation of gout
2 The contribution of hyperuricemia for gout
3 The relationship between insulin-like growth factor-1 and gout
4 The relationship between triglyceride and gout
5 The research strategy and significance of this study
Materials and methods
1 Source of patients data
2 Diagnostic criteria of primary gout
3 Exclusion criteria
4 Research method
5 Statistical analysis
Results
1 Characte r-stics of gout patients and alterations of the indicators
2 Relationship between serum uric acid level and other indicators
3 Relationship between serum IGF-1 level and other indicators
Discussion
2 The significance of the relationship between serum uric acid level and other indicators
3 The significance of the relationship between serum IGF-1 level and other indicators
4 The importance of knowledge about the clinical significance of hyperuricemia
5 The limitations of this study
6 Conclusions
References
Part Ⅱ Effect and mechanism of triglyceride metabolism disorder induced by high uric acid
Inctroduction
1 The relationship between high uric acid and triglyceride
2 Current research progress of the relationship between high uric acid and triglyceride
3 Related signaling pathways affecting lipid metabolism
4 The strategy,purpose，and significance of this study
Materials and methods
3 Oil red O staining
4 Determination of uric acid concentration
5 Determination of triglyceride concentration
6 Determination of Ketone body concentration
7 Immunohistochemical staining
8 Real-time RT-PCR analysis
9 Western blot assay
10 Statistical analysis
Results
1 Establishment of cell model and mouse animal model of uric acid-induced dyslipidemia
2 Effect of uric acid stimulation on triglyceride level alterations
3 Effect of uric acid stimulation on ketone body level alterations
4 Effects of uric acid stimulation on the alterations of lipid metabolism enzymes
5 Effect of uric acid stimulation on intracellular signaling pathway
Discussion
1 The significance of exploring the relationship between high uric acid and triglyceride
2 The effect of high uric acid on triglyceride
3 The way of high uric acid affects triglyceride
4 Cellular signaling pathway of high uric acid affects triglyceride
5 Conclusions
References
Part Ⅲ IGF-1 improves lipid metabolism disorder induced byhigh uric acid through IRS1／PI3K signaling pathway
Inctroduction
3 Biological actions of IGF-1 through IRS1／PI3K signaling pathway
4 The strategy，purpose，and significance of this study
Materials and methods
3 Detection of serum uric acid level in mice
4 Effect of IGF-1 on high uric acid induced abnormal ketone body level
5 Detection and analysis of effect of IGF-1 on changes of lipid metabolism enzymes caused by high uric acid
6 Effect of IGF-1 on lipid metabolism regulation and abnormal expression of transcription factors induced by high uric acid
8 Statistical analysis
Results
1 IGF-1 ameliorates high uric acid induced triglyceride elevation
2 IGF-1 improves high uric acid induced ketone body decrease
3 IGF-1 improves the expression of lipid metabolism enzymes with high uric acid simulation
4 IGF-1 improves the expression of lipid metabolism transcription factors with high uric acid challenge
5 IGF-1 attenuates the interference of hyperuricemia on IRS1／PI3K／Akt signaling pathway
Discussion
1 The discovery of the present study and its significance
2 The role of IGF-1 in lipid metabolism through IRS1／PI3K／Akt signaling pathway
3 The relationship between oxidative stress and triglyceride metabolism disorder
4 The inhibitory effect of high uric acid on oxidative metabolism of fatty acids
5 Conclusions
References
攻读学位期间发表的学术论文
致谢
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山东大学;
