Torres V E, Bengal R J, Nickander K K, Grande J P, Low P A
Department of Nephrology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Am J Kidney Dis. 1998 Apr;31(4):687-93. doi: 10.1053/ajkd.1998.v31.pm9531187.
A gender-associated dimorphism, with males being more severely affected than females, has been observed in autosomal dominant polycystic kidney disease, acquired renal cystic disease, and the renal cystic disease of the Han:SPRD rat. A recent study has suggested that gonadal hormones may be responsible for this dimorphism. Because gonadal hormones have an effect on the concentration of alpha-tocopherol in the liver and adrenal glands and because recent studies indicate that oxidative stress may be important in the pathogenesis of polycystic kidney disease, we wanted to determine whether the renal concentration of alpha-tocopherol is higher in female than in male rats and whether this difference accounts for the gender dimorphism of polycystic kidney disease in Han:SPRD rats. At 3 weeks of age, male and female heterozygous cystic (cy/+) rats were divided into three groups fed a vitamin E-deficient diet or the same diet supplemented with either 65 IU or 10,000 IU alpha-tocopherol/kg laboratory chow. At 8 weeks of age, blood samples and kidneys were obtained for determinations of plasma creatinine and urea, renal concentration of alpha-tocopherol and glutathione, kidney weights, and histomorphometric analysis. Female rats had higher renal concentrations of alpha-tocopherol and less severe renal cystic disease, as reflected by plasma creatinine and urea values, kidney weight corrected by body weight, and histomorphometric analysis, than male rats. The difference in renal alpha-tocopherol concentration, however, could not account for the different severity of the renal cystic disease, because depletion or enrichment of vitamin E in the diet had marked effects on the renal concentration of alpha-tocopherol without affecting the severity of the renal cystic disease. Cy/+ rats had higher renal concentrations of alpha-tocopherol than +/+ animals, possibly reflecting a disturbance of redox metabolism associated with polycystic kidney disease. Renal concentrations of glutathione were unaffected by the vitamin E content of the diet. Although these results do not support the use of vitamin E in the treatment of polycystic kidney disease, observations in the Han:SPRD rat may or may not be relevant to human polycystic kidney disease.
在常染色体显性多囊肾病、获得性肾囊肿病以及Han:SPRD大鼠的肾囊肿病中，观察到一种与性别相关的二态性，即雄性比雌性受影响更严重。最近一项研究表明，性腺激素可能是造成这种二态性的原因。由于性腺激素会影响肝脏和肾上腺中α-生育酚的浓度，且最近的研究表明氧化应激在多囊肾病的发病机制中可能起重要作用，因此我们想确定雌性大鼠肾脏中α-生育酚的浓度是否高于雄性大鼠，以及这种差异是否能解释Han:SPRD大鼠多囊肾病的性别二态性。3周龄时，将雄性和雌性杂合囊性（cy/+）大鼠分为三组，分别喂食缺乏维生素E的饲料，或添加了65 IU或10,000 IUα-生育酚/千克实验室饲料的相同饲料。8周龄时，采集血样和肾脏样本，用于测定血浆肌酐和尿素、肾脏中α-生育酚和谷胱甘肽的浓度、肾脏重量以及组织形态计量分析。与雄性大鼠相比，雌性大鼠肾脏中α-生育酚的浓度更高，肾囊肿病也较轻，这一点通过血浆肌酐和尿素值、按体重校正后的肾脏重量以及组织形态计量分析得以体现。然而，肾脏α-生育酚浓度的差异并不能解释肾囊肿病严重程度的不同，因为饲料中维生素E的缺乏或富集对肾脏α-生育酚的浓度有显著影响，但并未影响肾囊肿病的严重程度。Cy/+大鼠肾脏中α-生育酚的浓度高于+/+动物，这可能反映了与多囊肾病相关的氧化还原代谢紊乱。饲料中维生素E的含量对肾脏谷胱甘肽的浓度没有影响。尽管这些结果不支持将维生素E用于治疗多囊肾病，但在Han:SPRD大鼠中的观察结果可能与人类多囊肾病相关，也可能无关。
