不同剂量乌司他丁对庆大霉素急性肾损伤的影响

Effects of Different Doses of Ulinastatin on Acute Kidney Injury Induced with Gentamicin in Rats

目的:观察不同剂量乌司他丁(UTI)对大鼠急性肾损伤(AKI)的保护作用。方法:36只SD大鼠随机分为假手术组、模型组、治疗Ⅰ组、治疗Ⅱ组、治疗Ⅲ组和治疗Ⅳ组,每组6只。腹腔注射庆大霉素制备AKI模型。治疗Ⅰ、Ⅱ、Ⅲ和Ⅳ组连续7 d分别经腹腔注射乌司他丁10 000、30 000、50 000和100 000 U·kg-1·d-1。第8天留取标本观察血胱抑素C(Cys C)、尿液肾损伤分子-1(Kim-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)浓度,HE染色观察肾组织病理学改变并行半定量评分。结果:模型组Cys C、Kim-1、NGAL、肾组织病理学评分均较假手术组升高,治疗组上述指标均较模型组下降,而治疗Ⅱ组上述指标低于治疗Ⅰ组(P<0.05或0.01),治疗Ⅲ组、Ⅳ组和治疗Ⅱ组间的差异无统计学意义。结论:30 000 U·kg-1·d-1UTI可以减轻庆大霉素急性肾损伤,更大剂量不增强其肾脏保护作用。

Objective To investigate the effects of different doses of ulinastatin against acute kidney injury(AKI) induced with gentamicin in rats.Methods Thirty-six male rats were randomly divided into sham group,model group and treatment group Ⅰ,Ⅱ,Ⅲ,Ⅳ(n = 6).Rat models of AKI were established by intraperitoneal injection of gentamicin for 7 days.Ulinastatin was intraperitoneally injected in treatment group Ⅰ,Ⅱ,Ⅲ and Ⅳ for 7 days with a dose of 10 000 U·kg-1· d-1,30 000 U·kg-1·d-1,50 000 U·kg-1·d-1and 100 000 U·kg-1·d-1,respectively.The serum concentrations of cystatin C(Cys C),urine kidney injury molecule(Kim-1) and neutrophil gelatinase associated lipocalin(NGAL) were detected on eighth day.The renal pathological changes were observed and semiquantitative score was performed.Results Compared with model group,the serum levels of Cys C,Kim-1 and NGAL,the score of renal pathology were significantly increased in sham group,but decreased in treatment groups.The above indexes in treatment groupⅡ were significantly lower than those of treatment groupⅠ(P < 0.05 or P < 0.01),meanwhile,no significant difference were found between treatment groupⅡ and treatment group Ⅲ,Ⅳ.Conclusion Ulinastatin could alleviate gentamicin-induced AKI in rats at a dose of 30 000 U·kg-1·d-1,and a high dose of ulinastatin cannot enhance its protection on renal function.