Chan L, Shapiro J I
University of Colorado School of Medicine, Department of Medicine, Denver.
Ren Physiol Biochem. 1989 May-Jun;12(3):181-90. doi: 10.1159/000173192.
In the last few years, we have focused our research effort on the magnetic resonance spectroscopic (NMR) studies of organ transplantation in the rat. P-31 NMR was employed to study changes in high-energy phosphates, intracellular pH in vivo of transplanted kidneys either during normal function, while undergoing the rejection process or subjected to other insults (e.g. ischemia, cyclosporine nephrotoxicity, urinary obstruction) which may also cause graft dysfunction. Nuclear magnetic resonance (NMR) parameters, specifically relative peak areas and intracellular pH, accurately distinguished among the different causes of graft dysfunction. Ureteral obstruction was clearly identified by elevations in the phosphodiester/urine phosphate peak. Ischemia and rejection were both associated with increases in inorganic phosphates and phosphomonesters and decreases in the beta-phosphate peak of adenosine triphosphate but were distinguishable from each other by differences in intracellular pH which was normal in rejected allografts (7.33 +/- 0.07, n = 3) and low in ischemic allografts (7.00 +/- 0.05, n = 3, p less than 0.05). Grafts insulted with cyclosporine toxicity were not distinguishable from normal allografts by any of the parameters studied. To determine the temporal relationship of NMR changes in allograft rejection, similar studies were performed serially in a group of rejecting (R) kidneys (n = 7) and compared with a control group of nonrejecting (NR) kidneys (n = 7). Major decrease in adenosine triphosphate (ATP) with increases in Pi and a marked increase in the Pi/ATP ratio were noted in the R allografts over time. The R allografts could be completely segregated from the NR allografts on the basis of the Pi/ATP ratio by day 7. These data suggest that 31P NMR spectroscopy may have potential clinical application in differentiating among the causes of graft failure of human renal allografts.
在过去几年中,我们将研究精力集中于大鼠器官移植的磁共振波谱(NMR)研究。采用磷-31 NMR来研究移植肾在正常功能期间、经历排斥过程或遭受其他可能导致移植物功能障碍的损伤(如缺血、环孢素肾毒性、尿路梗阻)时高能磷酸盐和细胞内pH值的变化。核磁共振(NMR)参数,特别是相对峰面积和细胞内pH值,能够准确区分移植物功能障碍的不同原因。输尿管梗阻可通过磷酸二酯/尿磷酸盐峰的升高明确识别。缺血和排斥均与无机磷酸盐和磷酸单酯增加以及三磷酸腺苷的β-磷酸盐峰降低有关,但可通过细胞内pH值的差异相互区分,排斥的同种异体移植物细胞内pH值正常(7.33±0.07,n = 3),缺血的同种异体移植物细胞内pH值较低(7.00±0.05,n = 3,p<0.05)。受环孢素毒性损伤的移植物在研究的任何参数上与正常同种异体移植物均无差异。为了确定同种异体移植排斥中NMR变化的时间关系,对一组正在发生排斥反应的(R)肾脏(n = 7)进行了连续的类似研究,并与一组未发生排斥反应的(NR)肾脏(n = 7)对照组进行比较。随着时间的推移,R组同种异体移植物中三磷酸腺苷(ATP)显著减少,无机磷酸盐增加,Pi/ATP比值显著升高。到第7天,R组同种异体移植物可根据Pi/ATP比值与NR组同种异体移植物完全区分开来。这些数据表明,磷-31 NMR波谱在区分人类肾同种异体移植物功能衰竭的原因方面可能具有潜在的临床应用价值。