Moore K P, Taylor G W, Gove C, Wood J, Tan K C, Eason J, Williams R
Institute of Liver Studies, Kings College School of Medicine and Dentistry, Denmark Hill, England, United Kingdom.
Kidney Int. 1992 Jun;41(6):1543-8. doi: 10.1038/ki.1992.224.
The metabolism and synthesis of cysteinyl leukotrienes by the isolated perfused pig kidney has been investigated. Kidneys were maintained for up to six hours in a recirculating perfusion system by using an oxygenated Krebs-Henseleit buffer containing albumin and the perfluorinated oxygen carrier, FC-43. Perfusion pressure was maintained at 12-13.5 kPa, with perfusion flow rates of 150-250 ml/min resulting in a urine output of between 20-180 ml/hr. Infusion of 3H-LTC4 into the renal artery resulted in rapid and complete metabolism, with the major urinary metabolites comprising LTE4, omega-hydroxy-LTE4, omega-carboxy-LTE4 and N-acetyl-omega-hydroxy-LTE4. The capacity of the isolated kidney to synthesize cysteinyl leukotrienes was monitored by measuring urinary LTE4 excretion; there was a basal urinary excretion of LTE4 (median 43 pg/min, range 8-470 pg/min). Neither lipopolysaccharide or human recombinant tumor necrosis factor alpha had any effect on basal excretion. Treatment with the calcium ionophore A23187, however, resulted in a 38.1 +/- 9.6-fold increase in urinary LTE4 excretion. We conclude that the isolated pig kidney, in the absence of circulating cells, can synthesize cysteinyl leukotrienes in the absence of circulating cells, which can then undergo extensive oxidative metabolism.
已对离体灌注猪肾中半胱氨酰白三烯的代谢和合成进行了研究。通过使用含有白蛋白和全氟氧载体FC - 43的充氧Krebs - Henseleit缓冲液，在循环灌注系统中将肾脏维持长达6小时。灌注压力维持在12 - 13.5 kPa，灌注流速为150 - 250 ml/min，尿量为20 - 180 ml/hr。将³H - LTC4注入肾动脉会导致快速且完全的代谢，主要的尿代谢产物包括LTE4、ω - 羟基 - LTE4、ω - 羧基 - LTE4和N - 乙酰 - ω - 羟基 - LTE4。通过测量尿LTE4排泄量来监测离体肾脏合成半胱氨酰白三烯的能力；LTE4的基础尿排泄量（中位数为43 pg/min，范围为8 - 470 pg/min）。脂多糖或重组人肿瘤坏死因子α对基础排泄均无任何影响。然而，用钙离子载体A23187处理会导致尿LTE4排泄量增加38.1±9.6倍。我们得出结论，在没有循环细胞的情况下，离体猪肾能够合成半胱氨酰白三烯，随后这些白三烯可进行广泛的氧化代谢。
