Preventive Protective Effect Of PHD-inhibitor On Mice Kidneys With Acute Ischemia-reperfusion Injury: An Experimental Study

Objective:The purpose of this project is to explore the preventive protective effect of PHD-inhibitor on mice kidneys with ischemia-reperfusion injury, and study initially its possible mechanism. Methods:Acute renal ischemic injury model was established in male ICR mice(8-10W) by removing right kidney followed by clamping left renal pedicle for 50 min. Eighteen ICR mice(male♂,8-10W) were randomly divided into three groups: sham group, ischemia-reperfusion(IRI) group, and treatment group with prolyl hydroxylase inhibitor. 24h、48h before the modeling, mice of treatment group were administrated via oral PHI(160mg/kg)(dissolved in 0.5% asodium carboxyl methyl cellulose). Ischemia-reperfusion group was given the same dose of 0.5% asodium carboxyl methyl cellulose. Sham group was treated as same as IRI group without modeling. 72 hours after injury, blood and kidney were collected to detect concentration of blood urea nitrogen(BUN),to assess the degree of damage of renal pathology by PAS staining, to detect the expression of HIF-1α mRNA、VCAM1 mRNA in renal tissue by RT-PCR and HIF-1α protein by Western-blot. Results:(1) Compared with sham group, the level of BUN was significantly increase relative to the IRI group(P<0.01). In treatment group, the level of BUN was obviously decreased in contrast to IRI group(P<0.01).(2) The structure of renal tissue in sham group was essentially normal. In IRI group, we saw obvious degeneration and necrosis inside the renal tubular epithelial cells, and also found notable expansion of lumens( P<0.01).In contrast to IRI group, the pathomorphological changes were alleviated in treatment group(P<0.01).(3) HIF-1α, a molecule that is critically involved in proline hydroxylase inhibitors was elevated in treatment group kidneys but remained relative normal in IRI group(P<0.01). And the expression of VCAM1 was significantly different between the two groups. In addition, these two molecules are hardly expressed in the sham group. Conclusions:(1) The model of renal ischemia-reperfusion injury are set up successfully.(2) Prophylactic PHDI, can significantly reduce ischemia reperfusion renal injury in mice, the protective mechanism may be achieved by increasing the expression of HIF-1α in kidney tissue.