【作者】 于波；

【导师】 邢昌赢； 管又飞；

【作者基本信息】 南京医科大学 ， 肾脏内科， 2006， 硕士

【摘要】 慢性肾衰竭是一种严重威胁人民健康的疾病，肾小球硬化是慢性肾衰竭的重要致病因素。对于肾小球硬化机制的研究表明，肾小球局部脂质代谢异常可能在肾小球硬化的发生过程中有重要作用，旨在降低循环和肾脏局部脂质负荷的方法也发现可以减轻和延缓肾小球硬化的发生和发展，因而阐明肾脏脂质代谢机制对预防和治疗肾小球硬化具有重要的意义。已有的研究表明，脂质聚集在系膜细胞中会导致其转变成泡沫样细胞，引起肾小球硬化而丧失原有的功能，因此系膜细胞中的脂质代谢调节在肾脏中显得尤为重要。 本研究旨在探讨肝X受体(liver X receptor，LXR)在小鼠肾脏系膜细胞脂质代谢中的作用及机制。我们的研究发现LXR特异性激动剂T0901317刺激培养的家兔系膜细胞后，转染的ABCA1荧光素酶报告基因活性增加。而用T0901317处理培养的小鼠系膜细胞24小时后，基因芯片结果也显示ABCA1基因表达被上调。因此我们推测在小鼠肾小球系膜细胞中，LXR可能通过上调ABCA1的表达，发挥调节脂质代谢的作用。另外，由于ABCG1也是LXR的靶基因，且同ABCA1以相似的方式调节机体胆固醇的代谢，所以同时观察了在小鼠肾小球系膜细胞中LXR对ABCG1的调节作用。 方法：LXR具有两种亚型LXR α(和LXR β，为了评估LXR α和LXR β在肾脏的表达，我们用反转录-多聚酶链式反应(RT-PCR)分析了肾脏、新鲜分离的肾小球及系膜细胞中两种亚型的mRNA表达更多还原

【Abstract】 Glomerulosclerosis is a common pathophysiological process in chronic renal disease and is a risk factor for the progression of renal damage. Increasing evidence suggests that lipid metabolism plays an important role in the pathogenesis of glomerulosclerosis. Clinical studies indicate that correction of dyslipidemia frequently associated with renal disease may slow the progression of chronic renal failure. Thus, elucidation of the mechanisms by which dyslipidemia worsen glomerulosclerosis may help in developing novel therapeutic option for the treatment of glomerulosclerosis. Mesangial cells are phenotypically similar to vascular smooth muscle cells and macrophages. Lipid accumulation in mesangial cells have been found to lead to foam cell formation and glomerulosclerosis, suggesting mesangial cells play an important role in glomerular lipid homeostasis.Liver X receptors (LXRs) are members of the nuclear receptor superfamily and exist in two isoforms including LXRα and LXRβ. LXRs, which are activated by endogenous (oxysterol) or synthetic ligands (TO901317), bind to a characteristic DNA sequence designated LXRE via forming a heterodimer with the retinoid X receptor α (RXRα). LXRs function as sterol sensors and enhance transcription of an array of genes更多还原