乌司他丁对急性肾损伤大鼠肾脏内皮素-1与一氧化氮的影响

Effects of Ulinastatin on Renal Expression of Endothelin-1 and Nitric Oxide in Rats with Toxic Acute Kidney Injury

目的：观察乌司他丁对中毒性急性肾损伤（AKI）大鼠肾脏内皮素1（ET-1）和一氧化氮（NO）的影响。方法将24只雄性 SD 大鼠随机分为正常对照组、模型对照组和治疗组。第1-3天,模型对照组和治疗组大鼠皮下注射庆大霉素,制备中毒性 AKI 模型；正常对照组皮下注射0.9％氯化钠注射液。第4天开始,治疗组腹腔注射乌司他丁30000 U·kg^－1·d^－1,其他两组腹腔注射0.9％氯化钠注射液3 mL·kg^－1·d^－1,均连续7 d。于第11天检测3组血清肌酐（Cr）、胱抑素 C（Cys C）及尿液肾损伤分子-1（Kim-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）浓度,肾组织 ET-1、ET-1 mRNA 以及 NO、内皮型 NO 合酶（eNOS）、诱生型 NO 合酶（iNOS）、eNOS mRNA 和 iNOS mRNA 水平。结果与正常对照组比较,模型对照组血清 Cr、Cys C 和尿液 Kim-1、NGAL 浓度,肾组织 ET-1、ET-1 mRNA、NO、iNOS、iNOS mRNA 水平均升高（P〈0.01）；与模型对照组比较,治疗组血清 Cr、Cys C,尿液 Kim-1、NGAL 浓度,肾组织 ET-1、ET-1 mRNA、NO、iNOS、iNOS mRNA 水平均降低（均 P〈0.01）。3组 eNOS 与 eNOS mRNA 差异无统计学意义。结论乌司他丁通过下调肾组织 ET-1、iNOS 和 NO 发挥治疗大鼠中毒性 AKI 作用。

Objective To investigate the effects of ulinastatin on renal expression of endothelin-1 and nitric oxide （NO） in rats with toxic acute kidney injury（AKI）. Methods Twenty-four male SD rats were randomly divided into the normal control group,model control group and treatment groups, with 8 rats in each group. Except normal control group, rats were subcutaneously injected with gentamicin （300 mg·kg^-1 ·d^-1 ） for 3 days to establish a model of toxic AKI.Rats in the treatment group were intraperitoneally injected with a 7-day course of ulinastatin （30 000 U·kg^-1·d^-1 ） from the fourth day.While the other two groups were injected with 0.9% sodium chloride injection （3 mL·kg^-1·d^-1 ）. The serum level of creatinine and cystatin-C,urinary concentration of kidney injury molecule-1（Kim-1） and neutrophil gelatinase-associated lipocalin （NGAL）, level of endothelin-1 and NO,expression of endothelin-1 mRNA,endothelial nitric oxide synthase （eNOS）,induced nitric oxide synthase （iNOS）,eNOS mRNA and iNOS mRNA in homogenate of renal tissues in each group were detected on the eleventh day. Results Compared with the normal control group,serum level of creatinine and Cystatin-C,urinary concentration of Kim-1 and NGAL,level of endothelin-1 and NO,expression of endothelin-1 mRNA,iNOS and iNOS mRNA in homogenate of renal tissues were higher in model control group （P〈0.01, respectively）, while which were lower in treatment group than those in model control group （ P 〈 0. 01, respectively）. And no statistical significant difference of eNOS and eNOS mRNA expression in homogenate of renal tissues existed among the three groups. Conclusion Ulinastatin possesses curative role against rat with toxic AKI via down-regulating renal expression of endothelin-1,NO and iNOS.