MPO、NO在造影剂肾病中的表达及其与氧化应激的关系

Relationship between the expression of myeloperoxidase and nitric oxide in contrast-induced nephropathy and oxidative stress

目的观察MPO、NO在造影剂肾病大鼠模型中的表达,并探讨其与氧化应激的关系。方法 32只雄性SD大鼠,随机分为对照组(N)、造影剂组(CM)、肾损伤组(S)、造影剂肾病组(M),每组8只。脱水24h后,经股静脉间隔15分钟依次注射吲哚美辛(INDO,10mg/kg)、L-NG-硝基精氨酸甲酯(L-NAME,10mg/kg)和76%的复方泛影葡胺(DTZ,10ml/kg)建立造影剂肾病模型,继续脱水24h后处死大鼠。检测血肌酐(Scr)、尿素(Urea)、尿酸(UA)、内生肌酐清除率(Ccr)。肾皮质组织匀浆检测髓过氧化物酶(MPO)、谷胱甘肽过氧化物酶(GPX)、总超氧化物歧化酶(T-SOD)活性,一氧化氮(NO)、丙二醛(MDA)含量。观察肾脏组织病理学改变。结果 CM组与N组相比,肾功能、MPO、NO和氧化应激未见明显变化;M组与S组相比,Scr和Urea明显升高,Ccr显著降低,并且引起肾皮质GPX轻微降低(P>0.05),NO含量和T-SOD活性明显降低(P<0.05),MPO明显升高(P<0.05),而MDA在S组和M组较N组和CM组显著升高,但在S组和CIN组中并无显著性差异。形态学改变亦提示CIN病变最重。结论在已存在基础肾损伤时较正常条件下注射造影剂更易引起急性肾损伤及氧化应激状态改变,这可能与增加MPO、消耗NO,进一步激活NO信号通路有关。

Objective To investigate the expression Myeloperoxidase and Nitric oxide in contrastinduced nephropathy,and their relationship with oxidative stress. Methods 32 male Spragne - Dawley rats were randomly divided into four groups. They were control group （ N group, n = 8 ）, contrast medium group （ CM group, n = 8 ）, renal injury group （ S group, n = 8 ） and contrast - induced nephropathy group （ CIN group, n =8）. Following a 24 h dehydration, rats were injected with iv indomethacin （ 10 mg/kg） and iv L - NAME （ 10 mg/kg） 15 rain apart. After 15 min, diatrizoate （DTZ 10ml/kg） was injected into femoral vein. Another 24 h dehydration, rats were sacrificed and the venous blood was obtained to examine the serum creatinine （Scr）, urea, uric acid（UA） and calculate the creatinine clearance （Ccr） ; glutathione peroxidase （ GPX）, myeloperoxidase （ MPO）, total superoxide dismutase （ T - SOD）, nitric oxide（NO） and malonaldehyde （MDA） in renal cortex were were measured. Results CM group compared with the N group, renal function, MPO, NO and oxidative stress did not change. M group com- pared with the S group, Ser and Urea significantly increased, Cer significantly decreased GPX and cause a slight decrease in the renal cortex （ P 〉 0. 05 ）, NO levels and T - SOD activity was significantly lower （ P 〈 0. 05 ）, MPO was 1 higher （ P 〈 0. 05 ）, and MDA in the S group and M group than in the N group and CM group was significantly increased, but in the S group and the CIN group, there was no significant differenee. Morphological changes are the most important tips CIN lesions. Conclusion In comparison with normal conditions,the rats which have a basis of renal injury are more likely to cause contrast - induced nephropathy and the changes of oxidative stress, probably, associated with increased MPO, consumption of NO, further activation of NO signaling pathway.