Engelman R W, Wang B Y, Kinjoh K, El-Badri N S, Good R A
Department of Pediatrics, All Children's Hospital, University of South Florida, St. Petersburg 33701, USA.
Proc Soc Exp Biol Med. 1998 Jul;218(3):218-22. doi: 10.3181/00379727-218-44289.
Reduced dietary calories can delay the onset and diminish the severity of murine autoimmunities of numerous inbred and hybrid mutant strains. We sought to determine whether the precipitous, autoimmune, crescentic glomerulonephritis of recombinant inbred SCG/Kj mice could be abrogated similarly by calorie restriction. Weanling SCG/Kj mice develop hematuria and proteinuria, and 50% die as 16-week-old young adults. In this study, 113 4-week-old SCG/Kj mice were fed either ad libitum a milled chow (Group A, n = 50), or a semipurified diet (Group B, n = 29), or were fed a calorie-restricted semipurified diet (Group C, n = 34), so that mice of Group C consumed approximately 32% fewer calories, but similar amounts of essential dietary constituents as those of Group B. Calorie restriction of Group C provided modest (P = 0.05) or substantial survival advantage (P = 0.001) compared to the ad libitum feeding of Groups B or A, respectively. Progression to severe glomerular pathology was delayed among Group C mice, with more than a 5-week delay to heavy proteinuria (>100 mg/dl), a >4-week delay to hematuria, and a >5-week delay to median mortality, representing a 20% or 25% extension of median life span, compared to ad libitum-fed Group B and A mice, respectively. Mean glomerular histopathology scores were also lower in calorie-restricted mice compared to the ad libitum-fed cohorts (P = 0.001). Titers of anti-ss-DNA, ds-DNA, and ANCA autoantibodies developed in weanlings prior to the full imposition of calorie restriction and were not reduced significantly by calorie restriction.
减少饮食热量可以延缓多种近交和杂交突变品系小鼠自身免疫性疾病的发病，并减轻其严重程度。我们试图确定热量限制是否同样可以消除重组近交系SCG/Kj小鼠的急性自身免疫性新月体性肾小球肾炎。断乳后的SCG/Kj小鼠会出现血尿和蛋白尿，50%的小鼠在16周龄时死亡。在本研究中，113只4周龄的SCG/Kj小鼠，一组随意喂食碾碎的食物（A组，n = 50），一组喂食半纯化饮食（B组，n = 29），另一组喂食热量限制的半纯化饮食（C组，n = 34），C组小鼠摄入的热量比B组少约32%，但必需饮食成分的摄入量与B组相似。与B组或A组随意喂食相比，C组的热量限制分别提供了适度（P = 0.05）或显著的生存优势（P = 0.001）。C组小鼠严重肾小球病变的进展延迟，出现重度蛋白尿（>100 mg/dl）的时间延迟超过5周，出现血尿的时间延迟超过4周，中位死亡时间延迟超过5周，与B组和A组随意喂食的小鼠相比，中位寿命分别延长了20%或25%。与随意喂食的同组小鼠相比，热量限制组小鼠的平均肾小球组织病理学评分也更低（P = 0.001）。在完全实施热量限制之前，断乳小鼠体内抗单链DNA、双链DNA和抗中性粒细胞胞浆抗体的滴度就已出现，热量限制并未使其显著降低。
