| Objective:To investigate the affection of lipoxin A4 receptor agonist BML-111 on kidney function,HO-1 and PPAR-gamma expression in renal ischemia-reperfusion injury rats and to explore the intervention effect of BML-111 on acute renal ischemia-reperfusion injury and its internal mechanism..Methods:Thirty-five male SD rats were randomly divided into 7 groups: BML-111 treated model group（group B）,model group（group M）,normal control group（group N）,BML-111+Zn PP-treated model group（group Zn B）,Zn PP-treated model group（group Zn）,T0070907-treated model group（group T）,BML-111+T0070907-treated model group（group BT）.There were 5 rats in each group.Renal ischemia-reperfusion model was induced in all rats except the rats in normal control group.After a successful modeling 24 hours,the serum was collected for determination of serum creatinine（Scr）,blood urea nitrogen（BUN）,malondialdehyde（MDA）and urine glucosaminidase（NAG）.The kidney tissue were collected for determination histopathological changes,the expression of hemeoxygenase-1（HO-1）and Proliferator-activated receptor-γ（PPAR-γ）by immunohistochemical staining.The expressions of HO-1 and PPAR-γ in the renal cortex and medulla homogenates were analysed using Western blotting and reverse transcription-PCR.Results:The HE staining showed that in group N,there is no significant pathological changes in the structure of renal tissue,the BML-111 group and other five groups have varying degrees of damage and infiltration of inflammatory cells.Compared with group B,group M and the other four groups have more obvious renal tissue injury.Group Zn B and group BT compared with group Zn and group T found that the renal damage eased slightly.Compared with the group M,the levels of Scr,BUN,MDA and NAG in group B were significantly lower,the expression of HO-1/ PPAR-γ protein and m RNA increased（P<0.01）.Compared with group B,the levels of Scr,BUN,MDA and NAG in group Zn were significantly increased,the expression of HO-1/PPAR-γ protein and m RNA decreased（P<0.01）.Compared with group Zn,the levels of Scr,BUN,MDA,NAG in group Zn B were reduced to varying degrees,the expression of HO-1/PPAR-γ protein and m RNA increased（P<0.01）.Compared with group B,the levels of Scr,BUN,MDA and NAG in group T were significantly increased,the expression of HO-1/ PPAR-γ protein and m RNA decreased（P<0.01）.Compared with group T,the levels of Scr,BUN,MDA and NAG in group BT were significantly increased,the expression of HO-1/ PPAR-γ protein and m RNA decreased（P<0.01）.Conclusion:BML-111 can inhibit renal ischemia-reperfusion injury in rats and may have protective effect on renal function.Its mechanism is related to the regulation of HO-1/ PPAR-γ expression and inhibition of oxygen free radicals.There is a positive mutual influence correlationship between HO-1 and PPAR-gamma. |
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