增龄是雄性大鼠碘对比剂急性肾损伤的促进因素

Aging is an aggravating factor of iodinated contrast induced acute kidney injury in male rats

目的研究年龄对雄性大鼠碘对比剂急性肾损伤（CI．AKI）的影响。方法36只雄性SD大鼠根据月龄分为4月龄组、12月龄组和24月龄组，每组12只，各年龄组大鼠再随机分为正常对照组和对比剂组6个亚组，每组6只。禁水24h后，不同年龄鼠对比剂组大鼠尾静脉注射碘对比剂76％泛影葡胺（10ml／kg），相应对照组大鼠尾静脉注射等量生理盐水。检测尿肌酐（UCr）、尿N-乙酰-B．D．氨基葡萄糖苷酶（NAG）、血肌酐（SCr）、内生肌酐清除率（Ccr）、肾组织匀浆脂质过氧化物丙二醛（MDA）含量及血管紧张素转换酶（ACE）活性水平。48h后处死动物，观察肾脏的病理改变并检测。肾组织Sp1蛋白表达。结果注射对比剂后48h，24月龄鼠对比剂组SCr水平显著升高（P〈0．01），且升高幅度超过对照组的25％，Ccr明显下降（P〈0．05），肾组织匀浆ACE活性和MDA含量和肾小管损伤分数均明显增加（P〈0．01），肾组织Sp1蛋白的表达明显上调（P〈0．05）；注射对比剂后24h尿NAG酶活性明显较注射前24h增高（P〈0．001）。12月龄鼠注射对比剂组与相应对照组比较，Scr明显上升（P〈0．05），但升高幅度小于对照组的25％，肾组织匀浆MDA和ACE、肾小管损伤分数以及肾组织Sp1蛋白表达有上升趋势，但均无统计学意义（P〉0．05）。4月龄鼠注射对比剂组与相应对照组相比，上述各项指标比较均无统计学意义（P〉0．05）。结论增龄是雄性大鼠碘CI—AKI的促进因素，氧化性应激、ACE和核转录因子Sp1在老龄雄性大鼠碘CI-AKI发病机制中起一定作用。

Objective To study the effect of age on iodinated contrast induced acute kidney injury （CI-AKI） in male rats. Methods According to the age category, 36 healthy SD male rats were divided into three age groups （n=12/group）, including 4 months, 12 months and 24 months group, and then each age group were randomly divided into control group and contrast media（CM） group（n=6）. After 24h water deprivation, all three CM groups were intravascularly injected with 76% diatrizoate （10ml/kg） through a caudal vein. The other three control groups were injected with equal volumes of saline in parallel. Urine creatinine （UCr）, enzyme activity of urine N-acetyl-beta-D-glucosaminidase（UNAo）, serum creatinine （SCr）, creatinine clearance rate （Ccr）, malondialdehyde （MDA） level and angiotensin-converting enzyme（ACE） activity were determined. The rats were sacrificed after 48h. Then pathological changes of the right kidney tissue and the expression of Spl protein in the renal tissue were examined. Results At 48h after CM administration, 24 months rats showed a significant increase in SCr by 〉 25% from baseline （P 〈 0.01） and a decline in Ccr （P 〈 0.05）; the levels of ACE and MDA in renal tissues and scores of tubular injury were also increased （P 〈 0.01）; the expression of Spl protein in renal tissue was significantly upregulated （P 〈 0.05）. At 24h after CM administration, the enzyme activity of UNAG was significantly higher（P 〈 0.001 ）. In 12 months rats with CM injection, the level of SCr was increased by 〈25% from baseline（P 〈 0.05）. There was an increasing trend but no significant statistic difference in levels of MDA and ACE in renal tissue, scores of tubular injury, and expression of Spl protein between control group and CM group of 12 months rats. There was no difference between control group and CM group of 4 months rats in all above parameters （P〉0.05）. Conclusion Aging is a risk factor for CI-AKI in rat. Oxidative stress, ACE, and transcription factor Spl play a role in nephrotoxcity induced by iodinated contrast media in the aging male rats.