生物谷報道：南方醫(yī)科大學侯凡凡教授領導的研究團隊,，近期在腎臟病學權威國際期刊《美國腎臟病雜志》（J Am Soc Nephrol）和《國際腎臟病雜志》（Kidney Int）發(fā)表最新研究成果,。
他們發(fā)現,，患有慢性腎臟病的人血液中的主要蛋白質成分——白蛋白的結構會被某些氧化物質所改變，從而生成大量促進炎癥活性的氧化或糖化氧化修飾產物,。這些產物在血液和腎臟組織中堆積,，使腎臟病變加速,，最終導致腎臟功能的完全喪失（終末期腎衰竭）,。
侯凡凡等研究證實：給慢性腎臟病動物持續(xù)注射氧化修飾的白蛋白,，會使腎臟的慢性炎癥和纖維化明顯加重、腎功能迅速減退,；而抑制蛋白質氧化修飾產物的活性，能明顯改善腎臟結構和功能的異常,。這些表明蛋白質的氧化修飾產物,，是一類加速腎纖維化和腎臟病變發(fā)展的新致病因子。
研究還發(fā)現,，除血液白蛋白可能被修飾外,，食物中所含的蛋白質也可因煎,、炸、烤等高溫烹調處理發(fā)生糖化氧化修飾,。慢性腎臟病動物長期攝入含大量糖化氧化修飾蛋白的食物,，會使腎臟纖維化和腎功能減退的速度明顯增加。相反,，限制糖化氧化修飾蛋白的攝入,，可明顯抑制腎臟病變。短期臨床研究也證實,，避免食物的高溫烹調能明顯減少慢性腎臟病患者的尿蛋白排泄量,。這些研究結果提示，減少蛋白質的氧化或糖化氧化修飾可以作為慢性腎臟病防治的新靶標,。
慢性腎臟病是一組進行性發(fā)展的高死亡率,、高致殘率的疾病群，最終后果是發(fā)展至治療費用（透析,、腎移植）高昂的終末期腎衰竭,。因此，防止或延緩慢性腎臟病的發(fā)展,，是全球公共健康領域面臨的巨大挑戰(zhàn),。目前的臨床治療方法尚不能完全防止慢性腎臟病發(fā)展至腎衰竭，因此,，研究和尋找防治腎纖維化和腎臟病變進展的新靶標至關重要,。
原始出處一:
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: [email protected]
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.
