Silva P, Rosen S, Spokes K, Epstein F H
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Kidney Int. 1991 Apr;39(4):653-8. doi: 10.1038/ki.1991.78.
The addition of 2 mM glycine to the recirculating perfusate of isolated perfused rat kidneys almost completely prevented the severe morphological injury to tubular cells lining the medullary thick ascending limb (mTAL) that normally develops in this preparation. Glycine was similarly effective in reducing mTAL injury associated with hypoxic perfusion, indomethacin and amphotericin. Fractional reabsorption of sodium was increased with glycine, without any change in perfusate flow to the whole kidney and without consistent improvement in GFR. L-alanine demonstrated a similar though less pronounced cytoprotective action, but glutamine, cysteine, glutamate, cysteine plus glutamate, 1-serine and 4-aminoisobutyric acid all had little or no effect in preventing severe mTAL injury. The protective effect of glycine was unimpaired by the arginine analogue NG-monomethyl-l-arginine (L-NMMA), suggesting that the endothelial-derived relaxing factor, NO, was not involved. The action of glycine was not reduced by the addition of a substrate (benzoate) or a product (hippurate) of the glycine N-acyltransferase reaction. Glycine did not depress the respiration of dispersed mTALs prepared from rat kidneys. The cytoprotective effect of glycine in the mTAL of perfused kidneys, shared with l-alanine, appears to be relatively specific for these amino acids and probably unrelated to a diminution in cell work.
向离体灌注大鼠肾脏的循环灌注液中添加2 mM甘氨酸，几乎完全防止了髓质厚升支（mTAL）内衬的肾小管细胞出现严重的形态学损伤，而在该制备过程中这种损伤通常会发生。甘氨酸在减轻与低氧灌注、吲哚美辛和两性霉素相关的mTAL损伤方面同样有效。甘氨酸可增加钠的分数重吸收，而对全肾灌注流量无任何影响，且肾小球滤过率（GFR）也未持续改善。L-丙氨酸表现出类似但不太明显的细胞保护作用，而谷氨酰胺、半胱氨酸、谷氨酸、半胱氨酸加谷氨酸、L-丝氨酸和4-氨基异丁酸在预防严重的mTAL损伤方面几乎没有或没有作用。甘氨酸的保护作用不受精氨酸类似物NG-单甲基-L-精氨酸（L-NMMA）的影响，这表明内皮源性舒张因子NO未参与其中。添加甘氨酸N-酰基转移酶反应的底物（苯甲酸盐）或产物（马尿酸盐）不会降低甘氨酸的作用。甘氨酸不会抑制从大鼠肾脏制备的分散mTAL的呼吸。甘氨酸在灌注肾脏的mTAL中的细胞保护作用与L-丙氨酸相同，似乎对这些氨基酸具有相对特异性，并且可能与细胞工作的减少无关。
