Duffy Peter H, Lewis Sherry M, Mayhugh Martha A, Trotter Ronald W, Hass Bruce S, Thorn Brett T, Feuers Ritchie J
Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA.
Nutr Res. 2008 Mar;28(3):179-89. doi: 10.1016/j.nutres.2008.01.002.
This study evaluates the effects of age and chronic dietary restriction (DR) on nonneoplastic diseases in rats that were fed the American Institute of Nutrition (AIN)-93M purified diet. Male Sprague-Dawley (SD) rats were divided into an ad libitum (AL) group and a DR group that was fed the AIN-93M diet with intake reduced by 31%. Nonneoplastic disease profiles were developed to clarify whether the AIN-93M diet fulfills long-term nutritional requirements of rats. Subsets of rats were killed at 58 and 114 weeks of age, and histopathology was performed. At 58 weeks of age, the 2 main types of nonneoplastic diseases in AL rats were liver vacuolization and cardiomyopathy. Dietary restriction reduced the severity and incidence of both lesions. At 114 weeks of age, the most common lesions in AL rats were cardiomyopathy, nephropathy, liver vacuolization, and degeneration with renal failure and genitourinary infections causing the greatest mortality. Dietary restriction reduced the incidence and severity of these lesions. Nonneoplastic diseases accounted for 28.9% and 0.0% of total mortalities in the AL and DR groups, respectively; however, there was a higher incidence of unknown deaths in the DR rats (52.6%) compared to AL rats (28.9%), which may have limited the success of DR to improve survival. Although the AIN-93M diet supported chronic rat growth, alterations in some dietary component concentrations may be required to lower body weight in chronic rodent and human studies. Factors such as diet composition and digestibility may alter nonneoplastic diseases and mortality in rats and humans in a similar fashion.
本研究评估了年龄和长期饮食限制（DR）对喂食美国营养学会（AIN）-93M纯化日粮的大鼠非肿瘤性疾病的影响。雄性斯普拉格-道利（SD）大鼠被分为自由采食（AL）组和DR组，DR组喂食AIN-93M日粮，摄入量减少31%。制定非肿瘤性疾病概况以阐明AIN-93M日粮是否满足大鼠的长期营养需求。在58周和114周龄时处死部分大鼠，并进行组织病理学检查。在58周龄时，AL组大鼠的两种主要非肿瘤性疾病类型为肝空泡化和心肌病。饮食限制降低了这两种病变的严重程度和发生率。在114周龄时，AL组大鼠最常见的病变为心肌病、肾病、肝空泡化以及伴有肾衰竭和泌尿生殖系统感染的退化，这些导致了最高的死亡率。饮食限制降低了这些病变的发生率和严重程度。非肿瘤性疾病分别占AL组和DR组总死亡率的28.9%和0.0%；然而，与AL组大鼠（28.9%）相比，DR组大鼠的不明死亡发生率更高（52.6%），这可能限制了DR改善生存率的成功。尽管AIN-93M日粮支持大鼠长期生长，但在慢性啮齿动物和人体研究中，可能需要改变某些饮食成分的浓度以降低体重。饮食组成和消化率等因素可能以类似方式改变大鼠和人类的非肿瘤性疾病及死亡率。
