生物谷报道：南方医科大学侯凡凡教授领导的研究团队，近期在肾脏病学权威国际期刊《美国肾脏病杂志》（J Am Soc Nephrol）和《国际肾脏病杂志》（Kidney Int）发表最新研究成果。
他们发现，患有慢性肾脏病的人血液中的主要蛋白质成分——白蛋白的结构会被某些氧化物质所改变，从而生成大量促进炎症活性的氧化或糖化氧化修饰产物。这些产物在血液和肾脏组织中堆积，使肾脏病变加速，最终导致肾脏功能的完全丧失（终末期肾衰竭）。
侯凡凡等研究证实：给慢性肾脏病动物持续注射氧化修饰的白蛋白，会使肾脏的慢性炎症和纤维化明显加重、肾功能迅速减退；而抑制蛋白质氧化修饰产物的活性，能明显改善肾脏结构和功能的异常。这些表明蛋白质的氧化修饰产物，是一类加速肾纤维化和肾脏病变发展的新致病因子。
研究还发现，除血液白蛋白可能被修饰外，食物中所含的蛋白质也可因煎、炸、烤等高温烹调处理发生糖化氧化修饰。慢性肾脏病动物长期摄入含大量糖化氧化修饰蛋白的食物，会使肾脏纤维化和肾功能减退的速度明显增加。相反，限制糖化氧化修饰蛋白的摄入，可明显抑制肾脏病变。短期临床研究也证实，避免食物的高温烹调能明显减少慢性肾脏病患者的尿蛋白排泄量。这些研究结果提示，减少蛋白质的氧化或糖化氧化修饰可以作为慢性肾脏病防治的新靶标。
慢性肾脏病是一组进行性发展的高死亡率、高致残率的疾病群，最终后果是发展至治疗费用（透析、肾移植）高昂的终末期肾衰竭。因此，防止或延缓慢性肾脏病的发展，是全球公共健康领域面临的巨大挑战。目前的临床治疗方法尚不能完全防止慢性肾脏病发展至肾衰竭，因此，研究和寻找防治肾纤维化和肾脏病变进展的新靶标至关重要。
原始出处一:
Published ahead of print on January 3, 2007
J Am Soc Nephrol 18: 528-538, 2007
Pathophysiology of Renal Disease and Progression
Advanced Oxidation Protein Products Accelerate Renal Fibrosis in a Remnant Kidney Model
Hong Yan Li*, Fan Fan Hou*, Xun Zhang*, Ping Yan Chen, Shang Xi Liu*, Jian Xun Feng*, Zhi Qiang Liu*, Yue Xin Shan*, Guo Bao Wang*, Zhan Mei Zhou*, Jian Wei Tian* and Di Xie*
* Division of Nephrology, Nanfang Hospital, and Department of Biostatistics, Southern Medical University, Guangzhou, People’s Republic of China
Address correspondence to: Dr. Fan Fan Hou, Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, People’s Republic of China. Phone: 86-20-6164597; Fax: 86-20-87281713; E-mail: ffhou@public.guangzhou.gd.cn
Received for publication July 25, 2006. Accepted for publication October 26, 2006.
Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n = 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA- or vehicle-treated 5/6 Nx rats, AOPP RSA–treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.
