摘要
目的研究D-硝基精氨酸(D-NNA)对小鼠的肾损伤及其氧化应激机制。方法 ICR小鼠ig给予D-NNA150,50和15 mg·kg-1,连续30 d。测定并计算肾系数;血液生化分析仪检测血清中肌酐(Crea)和尿素氮(BUN);分光光度法测定肾组织一氧化氮(NO),硫代巴比妥酸法测丙二醛(MDA)含量,比色法测定谷胱甘肽过氧化酶(GSH-Px)和超氧化物歧化酶(SOD)活性;观察肾病理组织学变化。结果与5%葡萄糖对照组相比,D-NNA 150,50和15 mg·kg-1组血清中BUN分别明显升高了83.6%,36.2%和27.4%(P<0.05),D-NNA150和50 mg·kg-1组血清中Crea分别明显升高了281.6%和10.6%(P<0.05);D-NNA150 mg·kg-1组肾系数和NO水平分别明显降低了5.6%和25.5%(P<0.05);D-NNA150和50 mg·kg-1组肾组织中MDA水平分别明显升高了69.0%和36.9%(P<0.01),SOD活性和GSH-Px活性分别明显下降了17.4%和17.7%,7.3%和13.7%(P<0.05);D-NNA150 mg·kg-1组病理检查可见肾小管损伤,嗜碱性变,萎缩或囊性扩张和间质炎性浸润,D-NNA50和15 mg·kg-1组出现炎症细胞浸润。结论 D-NNA对小鼠肾有一定的损伤作用,其作用机制可能与D-NNA的手性转化产物L-NNA导致NO合成减少,产生ROS有关。
OBJECTIVE To explore the renal toxicity of NG-nitro-D-arginine（D-NNA） and oxidative stress mechanism.METHODS After D-NNA 150,50 and 15 mg·kg^-1 was ip given for 30 d,the kidney index,blood urea nitrogen（BUN） and creatinine（Crea） were assessed.The nitric oxide（NO） concentration,malondialdehyde（MDA） content,glutathione peroxidase（GSH-Px） and superoxide dismutase（SOD） activities in the renal cortex were determined and histopathological changes in renal tissues were detected.RESULTS Compared with 5% glucose control group,BUN in D-NNA 150,50 and 15 mg·kg^-1 groups increased by 83.6%,36.2% and 27.4%（P〈0.05）,respectively;Crea in D-NNA 150 and 50 mg·kg^-1 groups increased by 281.6% and 10.6%（P〈0.05）;the kidney index and NO concentration decreased significantly to 5.6% and 25.5% in D-NNA 150 mg·kg^-1 group;the MDA content increased significantly to 69.0% and 36.9%（P〈0.01） while SOD and GSH-Px activities decreased significantly to 17.4% and 17.7%（P〈0.01）,7.3% and 13.7%（P〈0.05） in D-NNA 150 and 50 mg·kg^-1 groups.Histopathology of mice showed renal tubular injury,basophilic change,atrophy,cystic expansion mild interstitial inflammatory infiltration in D-NNA 150 mg·kg^-1 group,but interstitial inflammatory infiltration in D-NNA 50 and 15 mg·kg^-1 groups.CONCLUSION D-NNA can induce renal toxicity,the mechanism of which may be due to the decreasing of NO content and increase of ROS induced by L-NNA which is a chiral inversion product of D-NNA.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2011年第3期275-279,共5页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金资助项目(30931759)
浙江省医药卫生科学研究基金资助项目(2009B001)
浙江省实验动物科技计划项目(2008F80001)~~
