Tomobe K, Philbrick D, Aukema H M, Clark W F, Ogborn M R, Parbtani A, Takahashi H, Holub B J
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
J Am Soc Nephrol. 1994 Dec;5(6):1355-60. doi: 10.1681/ASN.V561355.
The objective of these studies was to examine the effects of early dietary protein restriction on disease progression and survival in the DBA/2FG-pcy (pcy) mouse model of polycystic kidney disease. Male pcy mice of 70 days of age were fed either a normal protein (NP, 25% casein) or a low-protein (LP, 6% casein) diet for 105 days. At the end of the dietary treatment, kidney weight, kidney weight relative to body weight and kidney water contents were almost 50% lower, and relative renal phospholipid and triglyceride contents were almost 50% higher, in mice fed the LP diet, indicating a marked reduction in the progression of cystic disease. Morphometric analyses also revealed a lower total and percent cyst area in kidneys derived from mice on the LP compared with the NP diet. There were no significant differences in final body weight, urine volume and osmolality, GFR, proteinuria, or plasma levels of protein and urea between these two groups. In a second study, it was found that all mice fed an NP diet from 70 days of age onward had died by 310 days of age, compared with a 42% survival rate in LP-fed mice at this age. Overall, the mean lifespan for pcy mice on the LP diet was 24% longer than that for those mice on the NP diet (310 +/- 20 versus 251 +/- 16 days; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
这些研究的目的是在多囊肾病的DBA/2FG-pcy(pcy)小鼠模型中,检验早期饮食蛋白质限制对疾病进展和存活的影响。70日龄的雄性pcy小鼠分别给予正常蛋白质(NP,25%酪蛋白)或低蛋白质(LP,6%酪蛋白)饮食,持续105天。在饮食处理结束时,给予LP饮食的小鼠肾脏重量、肾脏重量相对于体重以及肾脏含水量降低了近50%,肾脏相对磷脂和甘油三酯含量则升高了近50%,这表明囊性疾病进展显著减缓。形态学分析还显示,与NP饮食组相比,LP饮食组小鼠肾脏的总囊肿面积和囊肿面积百分比更低。两组之间的最终体重、尿量和尿渗透压、肾小球滤过率、蛋白尿或血浆蛋白质和尿素水平均无显著差异。在第二项研究中,发现从70日龄开始给予NP饮食的所有小鼠在310日龄时均死亡,而此时给予LP饮食的小鼠存活率为42%。总体而言,LP饮食组pcy小鼠的平均寿命比NP饮食组小鼠长24%(310±20天对251±16天;P<0.01)。(摘要截短于250字)