尿KIM-1蛋白诊断早期造影剂肾病的实验研究

Value of urinary kidney injury molecule-1 protein in early diagnosis of radiocontrast-induced nephropathy in rats

目的测定大鼠尿液肾损伤分子-1(KIM-1)蛋白含量以研究其在造影剂肾病(RCIN)早期诊断中的价值。方法成年雄性SD大鼠72只随机分为A、B、C组(n=8)和D组(D组又分为2,6,12,24,48 h和7 d小组,n=8),采用尾静脉注射方法,每组注射3种药物,均间隔15 min。A组注射磷酸盐缓冲液(PBS)、生理盐水(NS);B组注射PBS、NS和造影剂(CM);C组注射吲哚美辛(INDO)、一氧化氮合酶抑制剂(L-NAME)和NS;D组注射INDO、L-NAME和CM。结果 D组大鼠给药6 h后血清肌酐(Scr)和尿素氮(BUN)含量显著升高(P<0.001),在给药24 h达到高峰,并于48 h基本恢复正常。组织学可见D组用药后6 h出现显著的病理学变化,出现小管间质弥漫性充血、出血,明显的肾小管坏死和肾小管结构消失;给药后12 h仍然存在显著的小管坏死,以及肾小管结构消失,但是小管间质充血出血程度减轻;给药后24 h肾髓质外带小管已经再生;给药后7 d时肾小管结构仍未完全恢复。D组给药后尿液KIM-1值和NAG值在各时间点均有不同程度升高,尿液KIM-1值在给药后2 h开始升高,24 h达高峰,并持续到7 d(P<0.001);尿液NAG值在6 h开始升高,48 h基本恢复正常;尿液MMP-9值在D组给药后各组均未见升高。结论测定大鼠尿KIM-1含量可以作为早期诊断RCIN的指标之一。

Objective To assess the value of determination of urine kidney injury molecule-1（KIM-1） protein content in the early diagnosis of radiocontrast-induced nephropathy（RCIN） in rats.Methods Seventy-two adult male SD rats were randomly divided into groups A,B,C（n=8） and D group（which was subdivided into 2,6,12,24,48 h and 7 days groups,n=8）.Group A was subject to injections via the tail vein of PBS and normal saline（NS）,group B received injections of PBS,NS,and contrast medium（CM）,group C with indomethacin（INDO）,nitric oxide synthase inhibitor（L-NAME）,and NS,and group D with INDO,L-NAME and CM.Each injection was given at the interval of 15 min.Results In group D,serum creatinine（Scr） and urea nitrogen（BUN） were significantly increased at 6 h after the injections（P0.001）,peaked at 24 h and recovered normal levels at 48 h.Histological examination revealed significant pathological changes in the kidneys at 6 h,showing diffuse tubulointerstitial hyperemia and hemorrhage,marked tubular necrosis and tubular structure destruction;at 12 h,significant tubular necrosis was still present with tubular structure destruction,but the tubulointerstitial hemorrhage was alleviated;at 24 h,tubular regeneration occurred in the renal medulla,but even till 7 days the tubular structures failed to show full recovery.In group D,urine KIM-1 level began to increase at 2 h,reached the peak level at 24 h,and lasted till 7 days（P0.001）;urine N-acetly-β-D-glucosaminidase（NAG） value began to increase at 6 h and became normal at 48 h.Urine MMP-9 level underwent no significant changes in group D over the time points of observation.Conclusion The results show that urinary KIM-1 levels can be used as an indicator for early diagnosis of RCIN.