Adiponectin protects the kidney from ischemia/reperfusion injury through PPAR-α induced HO-1 mechanism

• Main Authors: Yu-cheng Wang, 王裕正
• Other Authors: Heng Lin
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/82777946055188690628

碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 97 === Ischemia coupled with reperfusion (ischemia/reperfusion) in the kidney results in cell death, which can ultimately lead to severe renal injury. In patients with severe renal injury, the levels of adiponectin (APN), a member of adipocyte-derived cytokine, and its isoforms are increased. Adiponectin is known to exert anti-inflammatory and anti-apoptotic effects. However, the physiological function of adiponectin in severe renal disease is not clear. We have previously shown that serum adiponectin was greatly reduced in mice kidney I/R model serum. In this study, we further demonstrated that I/R-induced renal dysfunction, as evidenced by elevated serum creatinine and urea levels, was significantly reduced following i.v. injection of E. Coli carrying active with adiponectin, suggesting that adiponectin may play a protection role for kidney upon I/R. On pathology examination, we observed that adiponectin treated mice had more mild renal damage with renal cell disruption, tubular cell apoptosis, and neutrophil infiltration than sham operated mice. Furthermore, we found that administration of adiponectin to peroxisome proliferators activated receptor (PPARα) siRNA treated cells or PPARα knockout mice activated heme oxygenase-1 (HO-1) expression via PPARα-dependent pathway. Collectively, these results demonstrated that adiponectin reverses I/R-mediated renal tubule cell death through an PPARα-induced HO-1 mechanism, which may thus have therapeutic potential for diminishing I/R-dependent kidney injury and inflammation.