中文摘要：

目的 观察白三烯B4受体1（leukotriene B4 receptor 1,BLT1）拮抗剂U75302对顺铂导致的小鼠急性肾损伤（Acute Kidney Injury,AKI）的保护作用,并探讨可能的抗炎机制.方法8周龄健康雄性C57BL/6小鼠随机分组为：正常对照组、U75302对照组、顺铂处理组、顺铂＋U75302处理组,每组6只.其中顺铂处理组及顺铂＋U75302处理组于第0天给予顺铂20 mg/kg,U75302对照组及顺铂＋U75302处理组于第0、2天两次给予U75302 5μg/只.顺铂给药后3d处死小鼠,检测各组小鼠血清BUN、Scr水平,PAS糖原染色法观察肾脏病理改变,流式细胞术检测肾脏中浸润的炎症细胞数量,比色法检测肾组织匀浆MPO活性,抽提各组小鼠肾组织总RNA,实时荧光定量PCR检测肾组织炎症因子TNF-α、IL-1β及趋化因子CXCL1、CXCL2基因表达水平.结果 顺铂给药后3d,顺铂处理组小鼠血清BUN、Scr水平高于正常对照组（均P＜ 0.01）;并出现明显的肾脏病理损伤;肾脏中浸润的炎症细胞包括中性粒细胞、巨噬细胞、CD4＋T淋巴细胞、CD8＋T淋巴细胞,数量明显增多（均P＜0.01）;肾组织匀浆中MPO活性明显上升（P＜0.01）;肾组织炎症因子TNF-α、IL-1β,趋化因子CXCL1、CXCL2基因表达明显上调（均P＜ 0.01）.与顺铂处理组相比,顺铂＋U75302处理组血清BUN改变减少[（17.75±1.80） mmol/L比（42.6±6.66） mmol/L,P＜0.05],肾脏病理损伤减轻,肾脏中浸润的中性粒细胞、巨噬细胞数目减少[（146±13）×103/g比（296±66）×103/g,P＜0.05]、[（245±13）×103/g比（420±78）×103/g,P＜0.05],肾组织匀浆中MPO活性上升不明显[（1.756±0.283） U/g比（3.308±0.577） U/g,P＜0.05],肾组织炎症因子TNF-α、IL-1β,趋化因子CXCL1、CXCL2基因表达增加程度降低.结论 BLT1拮抗剂U75302对顺铂导致的小鼠AKI具有保护作用,其保护机制与减少肾脏炎症细胞浸润,抑制肾脏炎症反应有关.

英文摘要：

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.