摘要
目的探讨乌司他丁对大鼠中毒性急性肾损伤(AKI)的治疗作用及其机制。方法 24只SD雄性大鼠分为对照组、模型组和治疗组,每组大鼠8只。模型组和治疗组连续3d皮下注射庆大霉素(300mg·kg-1·d-1)建立大鼠中毒性AKI模型,第4天治疗组开始腹腔连续注射乌司他丁(30 000U·kg-1·d-1)7d。3组大鼠在第11天检测血清肌酐(Cr)和胱抑素C(Cys C)水平,尿液肾损伤分子-1(Kim-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平,观察肾脏病理学变化并行肾小管损伤半定量评分,检测肾组织匀浆丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)活性以及肿瘤坏死因子α(TNF-α)和IL-1β浓度。结果与对照组相比,模型组肾小管上皮细胞变性,肾小管囊腔扩张,管型形成,肾间质炎症细胞浸润,肾小管损伤半定量评分、血清Cr和Cys C,尿Kim-1和NGAL,肾组织MDA、TNF-α和IL-1β水平升高,SOD和GSH-Px活性下降。与模型组相比,治疗组肾脏病理改变减轻,肾小管损伤半定量评分、血清Cr和Cys C,尿液Kim-1和NGAL,肾组织MDA、TNF-α和IL-1β水平降低,SOD和GSH-Px活性升高。结论乌司他丁通过抑制肾组织氧化应激,下调促炎症因子水平,治疗大鼠中毒性AKI。
Objective To explore the curative effect of ulinastatin against toxic acute kidney injury（AKI） in rats and its mecha-nism .Methods Twenty-four male SD（Sprague Dawley） rats were randomly divided into 3 groups ,control group ,model group and treatment group with 8 rats in each group .Rats were subcutaneously injected gentamicin（300 mg/kg of body weight per day） for 3 days to establish models of toxic AKI .Rats in treatment group were intraperitoneally injected with a 7-day course of ulinastatin（30 000 U/kg of body weight per day） from 4th day .Dectetion of serum level of creatinine and Cystatin-C（Cys C） ,urinary concentra-tion of kidney injury molecule-1 （Kim-1 ） and neutrophil gelatinase-associated lipocalin （NGAL ） ,activity of superoxide dismutase （SOD） and glutathione peroxidase（GSH-Px） ,content of malondialdehyde ,levels of tumour necrosis factor-alpha（TNF-α） and inter-leukin-1β（IL-1β） in homogenate of renal tissues as well as observation of renal pathological changes and semiquantitative score in each group were conducted on 11th day .Results In model group ,degeneration and necrosis of renal tubular epithelial cell ,dilatation of renal tubular cavity and inflammatory cell infiltration in renal interstitial were observed .Renal pathological changes were milder in treatment group ,when compared with the model group .Renal pathological semiquantitative score ,serum level of creatinine and Cys C ,urinary concentration of Kim-1 and NGAL ,content of malondialdehyde ,levels of TNF-α and IL-1β in homogenate of renal tissues were higher in model group than in control group ,while those in treatment group were lower than in model group（P〈0 .01 , respectively） .And activity of SOD and GSH-Px in homogenate of renal tissues were lower in model group than in control group ,and those in treatment group were higher than in model group and control group（P〈0 .01 ,respectively） .Conclusion Ulinastatin pos-sesses a curative role in toxic AKI in rat via inhibiting oxid
出处
《重庆医学》
CAS
CSCD
北大核心
2014年第29期3929-3931,3934,共4页
Chongqing medicine
基金
湖北省教育厅科学技术研究项目(Q20092406)
