Haviv Y S, Wald H, Levi M, Dranitzki-Elhalel M, Popovtzer M M
Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120.
Pediatr Nephrol. 2001 May;16(5):412-6. doi: 10.1007/s004670100588.
The pathogenesis of renal phosphate (Pi) leak in Fanconi syndrome is unknown. Disorders of apical membrane transporters, leaky apical membrane, depleted cellular Pi and ATP, and impaired sodium (Na) pumps have been proposed as underlying defects. The present study examined the role of type II Na-Pi cotransport system (NaPi-2) in experimental Fanconi syndrome in rats. Following a single injection of maleic acid (MA), 75 mg/kg body weight i.p., rats were sacrificed after 90 min, 4 h, and 24 h. Renal cortical expression of NaPi-2 mRNA was determined by Northern blotting, and brush border membrane (BBM) NaPi-2 protein by Western blotting. Increased urinary excretion of phosphate was demonstrated as soon as 90 min after MA injection, and was sustained at 4 and 24 h, NaPi-2 mRNA expression and NaPi-2 protein were not decreased after 90 min. NaPi-2 mRNA decreased after 4 h, while NaPi-2 protein decreased only at 24 h. Hence, the immediate phosphaturia in experimental Fanconi syndrome may be independent of NaPi-2 downregulation, possibly resulting from energy depletion or membrane dysfunction. The decrease in NaPi-2 mRNA expression and the subsequent NaPi-2 protein decrease may account for the second-phase phosphaturia.
范可尼综合征中肾磷酸盐（Pi）漏出的发病机制尚不清楚。有人提出顶膜转运体异常、顶膜渗漏、细胞内Pi和ATP耗竭以及钠（Na）泵功能受损是潜在缺陷。本研究探讨了II型钠-磷共转运系统（NaPi-2）在大鼠实验性范可尼综合征中的作用。单次腹腔注射75 mg/kg体重的马来酸（MA）后，分别在90分钟、4小时和24小时处死大鼠。通过Northern印迹法测定肾皮质中NaPi-2 mRNA的表达，通过Western印迹法测定刷状缘膜（BBM）中NaPi-2蛋白的表达。MA注射后90分钟即出现尿磷排泄增加，并在4小时和24小时持续存在，90分钟后NaPi-2 mRNA表达和NaPi-2蛋白未降低。4小时后NaPi-2 mRNA降低，而NaPi-2蛋白仅在24小时降低。因此，实验性范可尼综合征中的即刻磷尿症可能与NaPi-2下调无关，可能是由于能量耗竭或膜功能障碍所致。NaPi-2 mRNA表达的降低以及随后NaPi-2蛋白的减少可能是第二阶段磷尿症的原因。
