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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 investigate the renal damage and oxidative stress mechanism of D-nitroarginine (D-NNA) in mice. Methods ICR mice were given D-NNA 150, 50 and 15 mg · kg-1 ig for 30 days. The serum creatinine (Crea) and blood urea nitrogen (BUN) were detected by blood biochemical analyzer. Nitric oxide (NO) in renal tissue was measured by spectrophotometry. Malondialdehyde (MDA) was measured by thiobarbituric acid method ), And the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were measured by colorimetric method. The histopathological changes of renal were observed. Results The serum levels of BUN in D-NNA 150, 50 and 15 mg · kg-1 groups were significantly increased by 83.6%, 36.2% and 27.4%, respectively (P <0.05) compared with 5% glucose control group Crea in serum of 50 mg · kg-1 group were significantly increased by 281.6% and 10.6%, respectively (P <0.05). The renal coefficient and NO level in D-NNA150 mg · kg-1 group were decreased by 5.6% and 25.5% P <0.05). The levels of MDA in renal tissue of D-NNA150 and 50 mg · kg-1 groups were significantly increased by 69.0% and 36.9% (P <0.01), while the activities of SOD and GSH-Px were decreased by 17.4% And 17.7%, 7.3% and 13.7%, respectively (P <0.05). In the group of D-NNA 150 mg · kg-1, renal tubular injury, alkalosis, atrophic or cystic dilatation and interstitial infiltration were observed. Inflammatory cell infiltration occurred in the NNA50 and 15 mg · kg -1 groups. Conclusions D-NNA may have a damaging effect on mouse kidney, and its mechanism may be related to the reduction of NO synthesis and ROS production by L-NNA, a chiral transformation product of D-NNA.