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长期果糖喂养与醛糖还原酶抑制:对正常大鼠肾脏多元醇途径的影响。

Prolonged fructose feeding and aldose reductase inhibition: effect on the polyol pathway in kidneys of normal rats.

作者信息

Bellomo G, Comstock J P, Wen D, Hazelwood R L

机构信息

Department of Biology, University of Houston, University Park, Texas 77004.

出版信息

Proc Soc Exp Biol Med. 1987 Dec;186(3):348-54. doi: 10.3181/00379727-186-42624.

DOI:10.3181/00379727-186-42624
PMID:3122222
Abstract

The effects of diets with differing carbohydrate composition on the kidney polyol pathway were investigated. The diets employed were F = fructose rich, G = glucose rich, S = cornstarch rich, and were fed for 30 days to six groups of 12 normal male Sprague-Dawley rats with and without addition of the aldose reductase inhibitor tolrestat (T). Fructose feeding resulted in higher kidney sorbitol levels (F = 0.847 +/- 0.152, G = 0.354 +/- 0.087, S = 0.207 +/- 0.041 microM/g wet wt, P less than 0.05). This was not observed in the tolrestat-treated animals (F + T = 0.182 +/- 0.024, G + T = 0.149 +/- 0.021, S + T = 0.152 +/- 0.020 microM/g wet wt). Aldose reductase activity was reduced with tolrestat administration (F = 0.0208 +/- 0.0023, F + T = 0.0048 +/- 0.0005; G = 0.0210 +/- 0.0002, G + T = 0.0059 +/- 0.0008; S = 0.0227 +/- 0.0022, S + T = 0.0062 +/- 0.0007 microU). Myoinositol levels did not differ among groups (F = 1.973 +/- 0.182, G = 2.291 +/- 0.307, S = 2.066 +/- 0.155 microM/g wet wt), but tended to increase with aldose reductase inhibition (F + T = 2.253 +/- 0.186, G + T = 2.713 +/- 0.166, S + T = 2.618 +/- 0.221 microM/g wet wt). Plasma glucose was higher in the fructose-fed rats (F = 10.78 +/- 0.55, G = 9.09 +/- 0.058, S = 9.03 +/- 0.52, F + T = 9.75 +/- 0.61, G + T = 8.42 +/- 0.64, S + T = 8.81 +/- 0.49 mM/liter). It is concluded that prolonged fructose feeding results in the accumulation of sorbitol in the kidney, caused by increased flux of glucose through the polyol pathway. This can be prevented by aldose reductase inhibition.

摘要

研究了不同碳水化合物组成的饮食对肾脏多元醇途径的影响。所采用的饮食为:F = 富含果糖,G = 富含葡萄糖,S = 富含玉米淀粉,并对六组每组12只正常雄性斯普拉格 - 道利大鼠喂食30天,其中部分组添加醛糖还原酶抑制剂托瑞司他(T)。喂食果糖导致肾脏山梨醇水平升高(F = 0.847±0.152,G = 0.354±0.087,S = 0.207±0.041微摩尔/克湿重,P < 0.05)。在接受托瑞司他治疗的动物中未观察到此现象(F + T = 0.182±0.024,G + T = 0.149±0.021,S + T = 0.152±0.020微摩尔/克湿重)。给予托瑞司他后醛糖还原酶活性降低(F = 0.0208±0.0023,F + T = 0.0048±0.0005;G = 0.0210±0.0002,G + T = 0.0059±0.0008;S = 0.0227±0.0022,S + T = 0.0062±0.0007微单位)。各组间肌醇水平无差异(F = 1.973±0.182,G = 2.291±0.307,S = 2.066±0.155微摩尔/克湿重),但随着醛糖还原酶抑制趋于升高(F + T = 2.253±0.186,G + T = 2.713±0.166,S + T = 2.618±0.221微摩尔/克湿重)。喂食果糖的大鼠血浆葡萄糖水平较高(F = 10.78±0.55,G = 9.09±0.058,S = 9.03±0.52,F + T = 9.75±0.61,G + T = 8.42±0.64,S + T = 8.81±0.49毫摩尔/升)。结论是,长期喂食果糖会导致肾脏中山梨醇积累,这是由葡萄糖通过多元醇途径的通量增加所致。这可通过抑制醛糖还原酶来预防。

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