艾替班特对多柔比星致大鼠急性肾损伤的保护作用及机制分析

Protective Effects and Mechanism of Icatibant on Doxorubicin Induced Acute Kidney Injury in Rats

目的:探讨缓激肽B2受体拮抗药艾替班特对多柔比星(Dox)致大鼠急性肾损伤的作用及机制分析。方法:30只大鼠随机分为对照组、Dox组和艾替班特组。除对照组外,各组均给予Dox 20 mg·kg^(-1) ip,艾替班特组再给予艾替班特180μg·kg^(-1) ip,连续3 d。后称取质量,取血测定SCr、BUN、白蛋白(Alb)和TG,取肾组织用于组织病理学检查,Western Blot技术检测肾脏组织FABP4表达。结果:Dox组大鼠体质量较对照组明显降低(P<0.05),艾替班特组和Dox组比较无明显变化(P>0.05)。与对照组相比,Dox组Alb明显降低,BUN、SCr和TG明显升高(P<0.01或P<0.05);与Dox组比较,艾替班特组Alb明显升高,BUN和SCr明显降低(P<0.05)。Dox组肾间质炎细胞浸润、充血,肾小管肿胀;艾替班特组较Dox组有所缓解。免疫组化结果显示FABP4主要表达于大鼠肾小管上皮细胞胞质,与对照组相比,Dox组FABP4蛋白表达明显增加(P<0.01);与Dox组相比,艾替班特组FABP4蛋白表达降低(P<0.05)。结论:艾替班特可减轻Dox所致大鼠急性肾脏损伤,其机制与脂代谢紊乱有关。

Objective:To investigate the effects and mechanism of Icatibant,a bradykinin B2 receptor antagonist,on doxorubicin induced acute kidney injury in rats.Methods:According to the principle of random grouping,30 experimental rats were divided into control group,doxorubicin group and Icatibant group.Except the control group,the other groups were i.p Dox 20 mg·kg^(-1).Icatibant treatment group i.p Icatibant 180μg·kg^(-1) for 3 consecutive days.After weighing,blood samples were collected to measure creatinine,urea nitrogen,albumin and triglyceride,and kidney tissues were collected for histopathological examination.The protein expression of FABP4 in kidney tissues was detected by Western blot.Results:The body weight was significantly decreased in doxorubicin group(P<0.05),while there was no significant change in Icatibant group.Compared with the control group,ALB in doxorubicin group was significantly decreased,the BUN,CREA and TG were significantly increased(P<0.01 or 0.05).Compared with doxorubicin group,ALB in Icatibant group was significantly increased,and BUN and CREA were significantly decreased(P<0.05).In doxorubicin group,the infiltration of renal interstitial inflammatory cells,congestion and renal tubule swelling were alleviated compared with those in doxorubicin group.Immunohistochemical results showed that FABP4 was mainly expressed in the cytoplasm of rat’s renal tubular epithelial cells.The protein expression of FABP4 in doxorubicin group was significantly increased(P<0.01),while that in Icatibant group was decreased(P<0.05).Conclusion:Icatibant can alleviate acute renal injury induced by doxorubicin in rats,and its mechanism is related to lipid metabolism disorder.