Abstract: 【Abstract】Objective To observe the dynamic changes of Klotho protein in acute kidney injury (AKI) during ischemia- reperfusion, and to further explore the role of Klotho protein in AKI. Methods A total of 120 Wistar male rats were randomly divided into Norm+NS group (normal rats + normal saline), Sham+NS group (sham operation + normal saline), Sham+Klotho group (sham operation +Klotho), I/R+NS group (ischemia-reperfusion + normal saline), and I/R+Klotho group (ischemia- reperfusion + Klotho) to establish the ischemia- reperfusion AKI groups and control groups. After the establishment of the models for 1h, 5h, 12h and 24h, six rats in each group were sacrificed. Blood urea nitrogen (BUN), serum creatinine (Scr), serum and kidney Klotho protein (ELISA method) and Klotho mRNA (RT-PCR method) were assayed. Pearson linear correlation method was used to analyze the relationship between serum and kidney Klotho protein levels and Scr level during AKI. Results After ischemia-reperfusion for 24h in I/R+NS group, Scr and BUN levels and renal tubular injury score increased as compared with those in Norm+NS group and Sham+ NS group (for Scr: t=3.767 and 4.145, P=0.013 and 0.009; for BUN: t=14.533 and 15.047, P<0.001; for renal tubular injury score: t=153.093 and 7.261, P<0.001 and t=0.008), and renal tubular epithelial cells showed significant degeneration and necrosis. In contrast in I/R+Klotho group in which exogenous Klotho protein was supplied, Scr and BUN levels and renal tubular injury score decreased (t=10.220, 9.571 and 11.076; P<0.001) and vacuolar degeneration of the renal tubular epithelial cells decreased, as compared with those in I/R+NS group. The content of Klotho protein and the expression of Klotho mRNA in sera and kidney tissues were lower in I/R+NS group than in Norm+NS group and Sham+NS group(P＜0.05). Conclusion In rats with ischemia-reperfusion AKI, Klotho protein and the expression of Klotho gene in serum and kidney decreased significantly. The decrease
of Klotho protein level is closely related to AKI. Klotho protein may be a protective factor for AKI.

Key words: Klotho protein, Ischemia-reperfusion renal injury, Acute kidney injury