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

在本研究中，我们研究了LOX-1在5/6肾大部切除(5/6 NX)大鼠中的表达和定位。与假手术组比较，5/6NX组大鼠6周后血压、血肌酐、血清胆固醇均显著升高。Northern印迹结果显示，5/6 NX大鼠全肾LOX-1mRNA水平明显高于对照组。多克隆抗LOX-1抗体免疫组织化学分析显示，5/6 NX大鼠肾小球部分细胞呈弱阳性，而肾小管内皮细胞和巨噬细胞等间质细胞呈强阳性，但肾小管未见染色。LOX-1在对照组大鼠中几乎为阴性。此外，初步结果表明，给予ATI拮抗剂坎地沙坦(10 mg/kg/d)可降低5/6 NX大鼠的LOX-1表达和血压。这些结果表明，LOX-1在慢性肾脏疾病模型大鼠的肾脏中表达上调，尤其是在间质细胞中，提示LOX-1的增加可能在间质和肾小球损伤的发展过程中起一定作用。

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.