乌司他丁对庆大霉素损伤的大鼠肾小管上皮细胞的保护作用  

Protective effect of ulinastatin against rat renal tubular epithelial cell injury induced by gentamicin

作　　者：沈建明[1] 勾荣[1] 田少江[1] 王黎萍[1] 刘艳红[2] 

机构地区：[1]湖北医药学院附属人民医院肾内科,湖北十堰442000 [2]湖北医药学院附属人民医院药学部,湖北十堰442000

出　　处：《现代预防医学》2015年第10期1826-1829,1863,共5页Modern Preventive Medicine

基　　金：湖北省教育厅科学技术研究项目(Q20092406)

摘　　要：目的观察乌司他丁对庆大霉素损伤的大鼠肾小管上皮细胞表达内皮素-1(ET-1)和一氧化氮(NO)的影响。方法传代培养大鼠肾小管上皮细胞(NRK-52E),分为对照组、损伤组(2 mg/ml庆大霉素)、治疗组A(2mg/ml庆大霉素+160 U/ml乌司他丁)、B(2 mg/ml庆大霉素+320 U/ml乌司他丁)和C(2 mg/ml庆大霉素+640 U/ml乌司他丁),观察各组细胞增殖能力、乳酸脱氢酶(LDH)水平、细胞凋亡率、ET-1和NO含量、内皮型一氧化氮合酶(e NOS)和诱生型一氧化氮合酶(i NOS)活性以及ET-1、e NOS和i NOS m RNA表达情况。结果与对照组相比,损伤组细胞增殖能力下降,LDH、细胞凋亡率、ET-1、ET-1 m RNA、NO、i NOS和i NOS m RNA表达均增多(P均<0.05)。与损伤组相比,治疗组细胞增殖能力增高,LDH、细胞凋亡率、ET-1、ET-1 m RNA、NO、i NOS和i NOS m RNA表达均减少;这些改变随剂量增加而明显(P均<0.05)。e NOS活性和m RNA表达在5组间的差异无统计学意义(P均>0.05)。结论乌司他丁通过抑制ET-1、NO和i NOS减轻庆大霉素损伤大鼠肾小管上皮细胞,这些作用在一定范围具有剂量依赖性。Objective The aim of this study was to investigate the effect of ulinastatin on the expression of endothelin-1 and nitric oxide in rat renal tubular epithelial cell injury induced by gentamicin. Methods The rat renal tubular epithelial cells（NRK-52E）were divided into the control group, the damage group（2 mg/ml gentamicin）, the treatment group A（2 mg/ml gentamicin plus 160U/ml ulinastatin）, B（2 mg/ml gentamicin plus 320 U/ml ulinastatin） and C（2 mg/ml gentamicin plus 640 U/ml ulinastatin）. The proliferation ability and apoptosis rate of the cell, the concentrations of lactate dehydrogenase（LDH）, endothelin-1 and nitric oxide（NO） in the supernatant of cell culture, the activity of endothelial nitric oxide synthase（e NOS） and inducible nitric oxide synthase（iNOS）, and the expression of endothelin-1, e NOS and iNOS mRNA were examined. Results In the damage group, proliferation ability was decreased, while the cell apoptosis rate, the concentrations of LDH, endothelin-1 and NO in cell culture supernatant, the activity of iNOS and the mRNA expression of endothelin-1 and iNOS were increased compared to the control group. Compared to the damage group, proliferation ability was increased, while the cell apoptosis rate, the concentrations of LDH, endothelin-1 and NO in cell culture supernatant, the activity of iNOS and the mRNA expression of endothelin-1 and iNOS were decreased in the treatment group, and all of the changes were dose-dependent of ulinastatin from 160 U/ml to 640 U/ml. And there was no statistical significant difference for the activity of e NOS and the expression of e NOS mRNA among five groups. Conclusion Ulinastatin, with a dose-dependent manner, alleviated rat renal tubular epithelial cell damage induced by gentamicin, via inhibiting ET-1, NO and iNOS.

关 键 词：乌司他丁 庆大霉素 肾小管上皮细胞 内皮素-1 一氧化氮 

分 类 号：R319[医药卫生—基础医学]