Martial S, Price S R, Sands J M
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
J Am Soc Nephrol. 1995 May;5(11):1971-8. doi: 10.1681/ASN.V5111971.
The regulation of mRNA for aldose reductase, sorbitol dehydrogenase, and the Na+/Cl-/taurine cotransporter was studied with three in vivo models in which urinary concentration is reduced: Sprague-Dawley rats undergoing a water diuresis or fed a low-protein diet or Brattleboro rats. In Sprague-Dawley rats, 3 days of water diuresis reduced inner medullary aldose reductase mRNA abundance 6.5-fold compared with untreated rats, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged. When water diuretic rats were acutely deprived of water, urine osmolality increased significantly after 4 h but aldose reductase mRNA did not increase until 12 h. Heat shock protein-70 mRNA was not increased by water deprivation. Second, in rats fed a low-protein diet for 3 wk, aldose reductase mRNA increased two-fold, whereas sorbitol dehydrogenase and taurine cotransporter mRNA were unchanged. Finally, in Brattleboro rats, urine osmolality and levels of aldose reductase and taurine cotransporter mRNA increased in response to 1 day of water deprivation, whereas sorbitol dehydrogenase mRNA was unchanged. Administering vasopressin (1 U/day) to Brattleboro rats for 8 days also increased urine osmolality and aldose reductase mRNA but did not alter sorbitol dehydrogenase or taurine cotransporter mRNA. This result is consistent with the hypothesis that changes in urine osmolality induce changes in aldose reductase mRNA abundance that are independent of vasopressin. It was concluded that, in rat inner medulla: (1) aldose reductase mRNA abundance varies with changes in water balance or dietary protein, whereas sorbitol dehydrogenase and taurine cotransporter mRNA do not; and (2) heat shock protein-70 mRNA abundance is not increased during acute osmotic stress.
利用三种使尿浓缩功能降低的体内模型，研究了醛糖还原酶、山梨醇脱氢酶和Na⁺/Cl⁻/牛磺酸共转运体的mRNA调控：进行水利尿或饲喂低蛋白饮食的Sprague-Dawley大鼠，或Brattleboro大鼠。在Sprague-Dawley大鼠中，与未处理的大鼠相比，3天的水利尿使髓质内醛糖还原酶mRNA丰度降低了6.5倍，而山梨醇脱氢酶和牛磺酸共转运体mRNA未发生变化。当水利尿大鼠急性缺水时，4小时后尿渗透压显著升高，但醛糖还原酶mRNA直到12小时才增加。热休克蛋白-70 mRNA并未因缺水而增加。其次，在饲喂低蛋白饮食3周的大鼠中，醛糖还原酶mRNA增加了两倍，而山梨醇脱氢酶和牛磺酸共转运体mRNA未发生变化。最后，在Brattleboro大鼠中，缺水1天后尿渗透压以及醛糖还原酶和牛磺酸共转运体mRNA水平升高，而山梨醇脱氢酶mRNA未发生变化。给Brattleboro大鼠连续8天注射血管加压素（1 U/天）也增加了尿渗透压和醛糖还原酶mRNA，但未改变山梨醇脱氢酶或牛磺酸共转运体mRNA。这一结果与尿渗透压变化诱导醛糖还原酶mRNA丰度变化且独立于血管加压素的假说一致。得出的结论是，在大鼠髓质内：（1）醛糖还原酶mRNA丰度随水平衡或饮食蛋白质的变化而变化，而山梨醇脱氢酶和牛磺酸共转运体mRNA则不然；（2）急性渗透应激期间热休克蛋白-70 mRNA丰度未增加。
