Molecular Mechanism of the role of oxidized LDL and physical stress in progressive renal disease

氧化低密度脂蛋白和身体应激在进行性肾病中作用的分子机制

• 批准号: 12671023
• 负责人: KANAME Shinya
• 金额: $ 2.18万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671023/
• 关键词: oxidized LDL; Lox-1; progressive renal disease; Dahlラット; 腎不全

In this study, we investigated LOX-1 expression and its localization in 5/6 subtotal nephrectomized (5/6 Nx) rats. 6 weeks after 5/6 Nx, blood pressure, serum creatinine and serum cholesterol were significantly increased compared with sham operated rats. Northern blot showed that LOX-1 mRNA levels in the whole kidney were markedly elevated in 5/6 Nx rats compared with control rats. Immunohistochemical analysis using polyclonal anti-LOX-1 antibody showed that in 5/6 Nx rats some glomerular cells were weakly positive, but interestingly, strong staining was widely observed in the interstitial cells including macrophages and peritubular endothelial cells, although there is no staining in the tubules. LOX-1 is almostjiegative in the control rats. Moreover, preliminary results showed that the LOX-1 expression decreased, as well as blood pressure, by administrating ATI antagonist candesartan (10 mg/kg/day) in 5/6 Nx rats. These results indicate that LOX-1 is upregulated in the kidney of rat model for chronic renal diseases, especially in the interstitial cells, suggesting that the increased LOX-1 might play some roles in the progression of interstitial and glomerular injury.

在这项研究中，我们研究了LOX-1的表达和其定位在5/6肾大部切除（5/6 Nx）大鼠。5/6 Nx治疗6周后，大鼠血压、血肌酐和血胆固醇水平均较假手术组显著升高。北方杂交结果显示，5/6只Nx大鼠全肾LOX-1 mRNA水平明显高于对照组。用多克隆抗LOX-1抗体的免疫组化分析显示，在5/6只Nx大鼠中，一些肾小球细胞呈弱阳性，但有趣的是，在间质细胞包括巨噬细胞和肾小管周围内皮细胞中广泛观察到强染色，尽管在肾小管中没有染色。对照组LOX-1几乎为阴性。此外，初步结果显示，在5/6只Nx大鼠中，通过给予ATI拮抗剂坎地沙坦（10 mg/kg/天），LOX-1表达降低，血压也降低。提示LOX-1在慢性肾脏病大鼠肾脏中表达上调，尤其是在间质细胞中，提示LOX-1的表达上调可能在间质和肾小球损伤中起一定作用。

项目成果

Nagase M., Kaname S., et al.: "Expression of Lox-1, an oxidized low-density lipoprotein receptor-1, in experimental hypertensive glomerulos clerasts"J. Am. Soc. Nephrol. 11. 1826-1836 (2000)

Nagase M.、Kaname S. 等人：“Lox-1（一种氧化低密度脂蛋白受体 1）在实验性高血压肾小球 clerass 中的表达”J.

Nagase M, Kaname S., et al.: "Expression of LOX-1, an oxidized low-densitylipoprotein receptor, in experimental hypertensive glomeruloselenosis"J. Am. Soc. Nephrol. 11. 1826-1836 (2000)

Nagase M、Kaname S. 等人：“氧化低密度脂蛋白受体 LOX-1 在实验性高血压性肾小球硬化症中的表达”J.

Nagase M, Kaname S, et al: "Expression of Lox-1, an oxidized low-densthy Eipoprotein receptn-1, In expeximental hypertensive Glomerular and Rats"J. Am. Soc. Nephrol. 11. 1826-1836 (2000)

Nagase M、Kaname S 等人：“Lox-1（一种氧化的低密度 Eipo 蛋白受体 1）在实验性高血压肾小球和大鼠中的表达”J。