高级蛋白氧化产物在血管钙化中的作用及其机制

项目名称： 高级蛋白氧化产物在血管钙化中的作用及其机制

项目编号： No.30800526

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 游怀舟

作者单位： 复旦大学

项目金额： 20万元

中文摘要： CKDⅤ#26399;患者普遍存在高AOPP血症和血管钙化，血浆AOPP水平与血管钙化密切相关。AOPP直接作用能使HASMC向成骨细胞分化，促进HASMC钙化。AOPP可能通过增加细胞内的氧化水平，和激活ERK通路促进平滑肌细胞向成骨细胞分化和促进钙化。 阿霉素肾病时同样存在氧化应激亢进，eNOS表达上调，尿N03- / N02-排泄增加。黄芪水提物能减轻蛋白尿，其机制可能是通过直接抑制阿霉素大鼠肾组织eNOS的过度表达，减少NO合成，以及提高抗氧化物酶活性，抑制自由基对肾组织的氧化损伤。 AKI患者的CRP/前白蛋白水平较健康对照和维持性血透患者明显升高。Cox回归分析显示CRP/前白蛋白是独立于年龄、性别、败血症和SOFA评分的死亡危险因素。CRP/前白蛋白水平可成为除SOFA评分以外的预计AKI患者预后的新指标。SGA评分是AKI患者全因死亡的独立危险因素。经年龄、性别、败血症和APACHII评分校正后，3-硝基酪氨酸和巯基仍是AKI患者90天死亡的独立危险因素。

中文关键词： 氧化应激；高级蛋白氧化产物；血管钙化；急性肾损伤；预后；

英文摘要： Increased plasma AOPP and vascular calcification were found in patients with CKD stage Ⅴ Plasma levels of AOPP were closely related to vascular calcification.AOPP directly increased the expression of osteoblastic differentiation markers including OPN and cbfαa key transcription factor in osteoblastic differentiation, and decreased the expression of smooth muscle cells contractile phenotype markers such as SM-αctin. These suggested that AOPP enhanced vascular calcification by promoting the osteoblastic differentiation of vascular smooth muscle cells.AOPP enhances in vitro osteoblastic differentiation and calcification of vascular smooth muscle cells through oxidative stress and ERK pathway. Oxidative stress and the expression of eNOS are increased in ADR nephropathy. ARE may decrease the proteinuria by suppressing the over expression of eNOS to decrease the NO production, and increasing the activities of antioxidase, inhibiting the oxidative injury of free radical to the kidney. Inflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to independent of the severity of illness and it may be a valuable addition to SOFA score to predict the prognosis of AKI patients. SGA score may be an independent risk factor for all-cause mortality within 90 days in patients with hospital-acquired acute kidney injury. There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content and diminished thiol content. 3-NT and thiol were associated with mortality of AKI patients independent of the severity of illness.

英文关键词： oxidative stress;advanced oxidation protein products;vascular calcification; acute kideny injury; prognosis;