GROWTH PATTERNS AND CLINICAL CHANGES IN RATS FED NIH-07 AND NTP-2000 DIETS

NIH-07开放式配方非纯化饲料已被选定的饮食， 自1980年以来的NTP啮齿动物研究。这种饮食是由20多个 年前，用于繁殖啮齿动物的繁殖、哺乳和生长 殖民地这种饮食含有大约24%的蛋白质，5%的脂肪和 在长期研究中，3.5%的纤维可能不是大鼠的最佳饮食， 某些组分如蛋白质、钙和磷的比例可以 增加慢性病的严重性。经过6年的 实验与不同配方的实验饮食，一个新的 配制指定为NTP-2000开放式配方非纯化饲料的饲料 用于啮齿动物的毒理学研究。这种饮食方式 来自NIH-07饮食，含有约15%的蛋白质，8.5%的脂肪和 9.5%的纤维。 这项研究的目的是比较1）生长模式，2） 血液学和临床化学参数，3）器官重量和4） Fischer 344（F344）大鼠中病变的发生率和严重程度 NIH-07和NTP-2000饮食13周。 每组25只6周龄的雄性和雌性F344大鼠饲喂NIH-07 或NTP-2000饮食13周。每周测量摄食量 间隔，在4、8和12周测定水消耗量， 在12周时进行血液学和临床化学评价。 治疗13周后，对大鼠进行尸检，解剖主要器官， 称重并通过以下方法评价主要器官的组织病理学变化： 光镜 雄性和雌性的生长模式基本相同， 节食。饲料消耗量略高， 对于喂食NTP-2000饲料的大鼠略低。男性的BUN值 和饲喂NTP-2000饲料的雌性动物的体重显著较低， 这种饮食的蛋白质含量。男性的胆固醇水平， 雄性和雌性动物的5 '核苷酸酶和碱性磷酸酶水平 NTP-2000略高，因为饲料中脂肪含量较高。 然而，饲喂NTP-2000饲料的雄性和雌性的甘油三酯水平 低于喂食NIH-07饮食的大鼠，尽管脂肪含量 NTP-2000饮食中的蛋白质含量高于NIH-07饮食中的蛋白质含量， 这可能是由于NTP-2000饮食的纤维含量较高。血清锌 饲喂NTP-2000饲料的雄性大鼠磷水平较低 这可能是由于较低的蛋白质、胱氨酸和磷浓度， NTP-2000饮食雄性和雌性大鼠的肝脏和肾脏重量 NTP-2000饲料喂养的大鼠显著低于NIH-07饲料喂养的大鼠 这种差异是由于NTP-2000饮食的蛋白质含量较低。 喂食NTP-2000饲料的大鼠肾上腺重量显著降低 比喂食NIH-07饮食的大鼠更高，这种差异的原因不是 知道的然而，为期两年的实验性饮食研究类似于 NTP-2000饮食引起肾上腺皮质激素的发生率显著下降， 嗜铬细胞瘤和较低的肾上腺重量可能与此有关 效果在13周研究中，F344大鼠最常见的病变是 肾钙质沉着症（皮质髓质交界处的矿化） 肾脏），肾病的初始变化，如肾脏 雄性中的小管再生和两性中的心肌病。的 NTP-2000饮食预防肾钙质沉着症，降低发病率， 肾病的严重程度和降低心肌病的严重程度。 总之，NTP-2000饮食1）对于生长是足够的， 维持大鼠，和2）似乎降低了发病率，严重程度 或延迟大鼠中饮食和年龄相关病变的发展。

NIH-07 open formula nonpurified diet has been the selected diet for the NTP rodent studies since 1980. This diet was formulated more than 20 years ago for reproduction, lactation and growth of rodents in breeding colonies. This diet which contains approximately 24% protein, 5% fat and 3.5% fiber may not be an optimal diet for rats in long-term studies, and some components such as protein, calcium and phosphorus ratio may be increasing the severity of chronic diseases. After 6 years of experimentation with different formulations of experimental diets, a new diet designated as NTP-2000 open formula nonpurified diet was formulated for rodents in toxicology studies. This diet is substantially different from NIH-07 diet and contains approximately 15% protein, 8.5% fat and 9.5% fiber. The purpose of this study was to compare 1) growth patterns, 2) hematology and clinical chemistry parameters, 3) organ weights and 4) incidence and severity of lesions in Fischer 344 (F344) rats fed the NIH-07 and NTP-2000 diets for 13 weeks. Groups of 25 male and female F344 rats of 6 weeks of age were fed NIH-07 or NTP-2000 diet for 13 weeks. Feed consumptions were measured at weekly intervals, water consumptions were determined at 4, 8 and 12 weeks, hematology and clinical chemistry evaluations were done at 12 weeks. After 13 weeks of treatment the rats were necropsied, major organs were weighed and histopathologic changes in major organs were evaluated by light microscopy. The growth patterns were essentially same for males and females fed both diets. The feed consumptions were slightly higher and water consumptions were slightly lower for rats fed NTP-2000 diet. The BUN values for males and females fed NTP-2000 diet were significantly lower due to lower protein content of this diet. The cholesterol level in males, and 5'nucleotidase and alkaline phosphatase levels in males and females fed NTP-2000 were slightly higher due to higher fat content of the diet. However, the triglyceride levels in males and females fed NTP-2000 diet were lower than the rats fed the NIH-07 diet even though the fat content of NTP-2000 diet was higher than in the NIH-07 diet and this difference may be due to higher fiber content of the NTP-2000 diet. The serum zinc and phosphorus levels of the male rats fed NTP-2000 diet were lower possibly due to lower protein, cystine and phosphorus concentrations of the NTP-2000 diet. The liver and kidney weights of male and female rats fed NTP-2000 diet were significantly lower than the rats fed NIH-07 diet and the difference is due to lower protein content of the NTP-2000 diet. The adrenal weights of rats fed NTP-2000 diet were significantly lower than the rats fed NIH-07 diet and the reason for this difference is not known. However, two-year studies with experimental diets similar to NTP-2000 diet caused a significant decrease in the incidence of adrenal pheochromocytomas and lower adrenal weights may be related to this effect. The most common lesions of F344 rats in 13-week studies are nephrocalcinosis (mineralization at corticomedullary junction of the kidney) in the females, initial changes of nephropathy such as renal tubule regeneration in males and cardiomyopathy in both sexes. The NTP-2000 diet prevented nephrocalcinosis, decreased the incidence and severity of nephropathy and decreased the severity of cardiomyopathy. In conclusion, the NTP-2000 diet 1) is adequate for growth and maintenance of rats, and 2) appears to decrease the incidence, severity or delay the development of diet and age associated lesions in rats.