ABSTRACT
Objective To investigate the effect of pretreatment with U75302,antagonist of leukotriene B4 receptor 1 (BLT1),on cisplatin induced acute kidney injury in mice and its immunoregulatory mechanism.Methods Healthy C57BL/6 mice were randomized into four subgroups:1.healthy control group;2.cisplatin group;3.U75302 control group;4.cisplatin + U75302 group,n=6.Group 2 and 4 received intraperitoneal injection of cisplatin (20 mg/kg) on day 0,group 3 and 4received intraperitoneal injection of U75302 (5 μg/mouse) on day 0 and day 2.Mice were sacrificed on the 3rd day and blood and kidney were collected.Renal function and histological changes were estimated,the infiltration of immune cells were determined by flow cytometry,the level of peroxidase (MPO) in kidney were determined by colorimetry,relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were detected by Real-time PCR.Results Compared with healthy control group,levels of BUN,Scr were higher in cisplatin group with serious tubular structural damage.There were more neutrophils,macrophages,CD4+ T lymphocytes,CD8+ T lymphocytes in kidneys of cisplatin group,the level of MPO and relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were also higher in cisplatin group.Compared with cisplatin group,lower BUN [(17.75±1.80) mmol/L vs (42.6±6.66) mmol/L,P ＜0.05],Scr were found in cisplatin+ U75302 group with less tubular structural damage.Meanwhile,U75302 reduced infiltration of neutrophils [(146±13)×103/g vs (296±66) ×103/g,P ＜ 0.05],macrophages [(245± 13)× 103/g vs (420±78)× 103/g,P ＜ 0.05] in the kidney.Levels of MPO [(1.756±0.283) U/g vs (3.308±0.577) U/g,P＜0.05] and relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were also lower.Conclusions BLT1 antagonist U75302 protects mice against AKI induced by cisplatin,and the mechanism is associated with reduced infiltration of inflammatory cells in kidney and the inhibition of kidney inflammation.