D-硝基精氨酸对小鼠肾损伤及氧化应激作用

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。

Renal toxicity and oxidative stress mechanism of NG-nitro-D-arginine on the kidney of mice

OBJECTIVE To explore the renal toxicity of N^G-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.