Gimelreich D, Popovtzer M M, Wald H, Pizov G, Berlatzky Y, Rubinger D
Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
Kidney Int. 2001 May;59(5):1812-20. doi: 10.1046/j.1523-1755.2001.0590051812.x.
Acute renal failure caused by ischemia followed by reperfusion is often associated with severe hyperkalemia. The present study was undertaken to characterize the effects of renal ischemia and reperfusion on plasma potassium (K) and on the gene expression of channel-inducing factor (CHIF), a putative K channel regulator, and of ROMK, the distal nephron secretory K channel.
The following groups of rats were studied: (1) sham operated (sham); (2) after one hour of ischemia by bilateral renal artery clamping (I), and after one hour of ischemia; (3) one hour of reperfusion (I-R 1 h); (4) 24 hours of reperfusion (I-R 24 h); (5) 48 hours of reperfusion (I-R 48 h); and (6) 72 hours reperfusion (I-R 72 h). The expression of CHIF and ROMK was examined by Northern blot hybridization in renal cortex, medulla, and papilla and in the colon. The abundance of ROMK protein was determined in the renal cortex and medulla by immunoblotting.
Maximal plasma creatinine and potassium levels after ischemia and reperfusion were 470 +/- 16 micromol/L, P < 0.0001 versus sham, and 9.65 +/- 0.33 mmol/L, P < 0.0001 versus sham, respectively. The expression of CHIF was significantly down-regulated in the medulla and papilla, with a maximal decrease of 80% at 48 to 72 hours. In contrast, a most significant increase in CHIF mRNA expression (250% of baseline) was noted in the colon after 24 to 48 hours of reperfusion. ROMK expression was reduced in the cortex and was completely abolished in the medulla at 48 to 72 hours of reperfusion. Ischemia and reperfusion injury significantly decreased ROMK protein abundance to 10% of control in the medullary fractions.
These results suggest that down-regulation of renal CHIF and ROMK may contribute at least partly to the hyperkalemia of acute renal failure after ischemia and reperfusion, while CHIF up-regulation in the colon may act as a compensatory mechanism of maintaining K balance via increased K secretion.
缺血后再灌注引起的急性肾衰竭常伴有严重高钾血症。本研究旨在探讨肾脏缺血再灌注对血浆钾（K）以及对通道诱导因子（CHIF，一种假定的钾通道调节因子）和ROMK（远端肾单位分泌性钾通道）基因表达的影响。
对以下几组大鼠进行研究：（1）假手术组（假手术）；（2）双侧肾动脉夹闭缺血1小时后（I），以及缺血1小时后；（3）再灌注1小时（I-R 1小时）；（4）再灌注24小时（I-R 24小时）；（5）再灌注48小时（I-R 48小时）；（6）再灌注72小时（I-R 72小时）。通过Northern印迹杂交检测肾皮质、髓质、乳头以及结肠中CHIF和ROMK的表达。通过免疫印迹法测定肾皮质和髓质中ROMK蛋白的丰度。
缺血再灌注后血浆肌酐和钾的最高水平分别为470±16微摩尔/升（与假手术组相比，P<0.0001）和9.65±0.33毫摩尔/升（与假手术组相比，P<0.0001）。CHIF在髓质和乳头中的表达显著下调，在48至72小时时最大降幅达80%。相反，再灌注24至48小时后结肠中CHIF mRNA表达显著增加（为基线的250%）。再灌注48至72小时时，ROMK在皮质中的表达降低，在髓质中完全消失。缺血再灌注损伤使髓质部分中ROMK蛋白丰度显著降至对照的10%。
这些结果表明，肾脏CHIF和ROMK的下调可能至少部分导致缺血再灌注后急性肾衰竭的高钾血症，而结肠中CHIF的上调可能是通过增加钾分泌来维持钾平衡的一种代偿机制。
