EFFECT OF LOVASTATIN ON THE DEVELOPMENT OF POLYCYSTIC KIDNEY-DISEASE IN THE HAN-SPRD RAT
EFFECT OF LOVASTATIN ON THE DEVELOPMENT OF POLYCYSTIC KIDNEY-DISEASE IN THE HAN-SPRD RAT
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DOI：
10.1016/0272-6386(95)90497-2
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发表时间：
1995-09-01
影响因子：
13.2
通讯作者：
GRANTHAM, JJ
中科院分区：
文献类型：
--
作者：
GILE, RD;COWLEY, BD;GRANTHAM, JJ
肾小管上皮细胞的增殖是导致汉族囊肿形成的主要因素：在患有常染色体显性多囊肾病（PKD）的SPRD大鼠中，ras蛋白在控制肾细胞增殖中是重要的，并且在PKD中res基因表达增加，焦磷酸法呢酯（乙酰辅酶A转化为胆固醇的中间体）是激活ras三磷酸鸟苷（GTP）结合蛋白所必需的，所述蛋白在执行几种细胞功能中是重要的，所述细胞功能包括细胞增殖、3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，如洛伐他汀、减少反应细胞中法呢基的产生，从而具有进一步改善PKD的加速上皮细胞增殖的潜力。我们对杂合子（Cy/+）Han：SPRD大鼠（4 mg/kg/d皮下注射）从4 - 10周龄给药洛伐他汀，这是这些动物囊性疾病快速进展的时期。未给药的雄性Cy/+大鼠比雌性大鼠出现更大的囊性肾，肾功能损害更严重，如先前报告的那样。在雄性动物中，洛伐他汀显著降低囊性肾大小（相对于体重）、囊肿体积密度和血清尿素氮水平，分别为14.5%、24.4%和25.6/%，雌性动物中的相应变化不显著，洛伐他汀对纯合子（+/+）正常雄性动物的肾脏重量或血清尿素氮无影响。根据这些结果，我们得出结论，洛伐他汀减少杂合子雄性汉：SPRD大鼠PKD的严重程度。(C)1995年由国家肾脏基金会，公司。
Proliferation of tubular epithelial cells is a major element leading to cyst formation in Han:SPRD rats with autosomal dominant polycystic kidney disease (PKD), ras proteins are important in the control of renal cell proliferation, and res gene expression is increased in PKD, Farnesyl pyrophosphate, an intermediate in the conversion of acetyl-CoA to cholesterol, is required for the activation of ras guanosine triphosphate (GTP)-binding proteins that are important in the execution of several cellular functions, including cell proliferation, 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, such as lovastatin, reduce farnesyl production in responsive cells and thereby have potential far ameliorating the accelerated epithelial cell proliferation of PKD. We administered lovastatin to heterozygous (Cy/+) Han:SPRD rats (4 mg/kg/d subcutaneously) from age 4 to 10 weeks, a period of rapid cystic disease progression in these animals, Untreated male Cy/+ rats developed larger cystic kidneys and had more severe renal functional impairment than females, as reported previously, In males, lovastatin significantly decreased cystic kidney size (referenced to body weight), the volume density of cysts, and the serum urea nitrogen level 14.5%, 24.4%, and 25.6/%, respectively, The corresponding changes in females were insignificant, and lovastatin had no effect on kidney weight or serum urea nitrogen in homozygous (+/+) normal male animals. On the basis of these results we conclude that lovastatin diminishes the severity of PKD in heterozygous male Han:SPRD rats. (C) 1995 by the National Kidney Foundation, Inc.