Abstract:

Objective

To establish and compare three animal models of acute kidney disease（AKD） to provide basic research evidence for investigating the pathophysiological mechanisms of AKD.

Methods

Ninety healthy male C57BL/6J mice aged 6-8 weeks were selected， and divided into model groups and control groups （15 mice/group） to establish three AKD models： folic acid model group （given intraperitoneal injection of 0.5% folic acid at 250 mg/kg）， folic acid control group （given intraperitoneal injection of the same amount of 0.3 M sodium bicarbonate）， unilateral ureteral obstruction （UUO） model group （given unilateral ureteral obstruction）， UUO control group （given sham operation）， unilateral ischemia-reperfusion （UIR） model group （given clamping of unilateral renal pedicle for 30 minutes）， and UIR control group （given sham operation）.On day 2， day 8， and day 14 after the modeling， samples were collected to measure serum creatinine， blood urea nitrogen， and proteinuria levels.Renal tissue pathology was observed， and renal injury and collagen deposition were assessed.Western blotting was used to detect the expressions of fibrosis-related proteins such as vimentin and α-smooth muscle actin.RT-qPCR was used to detect renal mRNA expressions of kidney injury molecule-1 （KIM-1） and inflammatory factors including TNF-α， IL-1β， IL-8， and IFN-γ）.

Results

In the folic acid model group， serum creatinine and blood urea nitrogen significantly increased at day 8 after the modeling （both P＜0.05）， while the KIM-1 expression was higher than those in the other two model groups at day 2 after the modelings.At day 8 after the modelings， the expression of KIM-1 in the UUO model group was higher than those in the other two model groups （all P＜0.05）.The tubular injury scores and collagen deposition in the three model groups showed a time-dependent increase， and were all higher than those in their respective control groups.At day 14 after modeling， the UUO model group showed higher tubular injury scores and collagen deposition， as well as higher expressions of vimentin and α-smooth muscle actin than the other two model groups （all P＜0.05）.At day 8 after the modelings， the mRNA expressions of IL-8， IL-1β， TNF-α， and IFN-γ in the three model groups were all higher than those in their respective control groups （all P＜0.05）， while the expressions of these inflammatory factors in the UUO model group were higher than those in the other two model groups （all P＜0.05）.

Conclusion

The folic acid model， UUO model， and UIR model of mice AKD were all established at day8after the modeling operations， among which the renal fibrosis during the disease progression was more severe in the UUO model.

Key words: Acute kidney diseases, Animal models, Folic acid, Unilateral ureteral obstruction, Ischemia-reperfusion