Barbosa Júnior A de A, Zhou H, Hültenschmidt D, Totovic V, Jurilj N, Pfeifer U
Centro de Pesquisas Conçalo Moniz (FIOCRUZ), Bahia, Brazil.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;61(6):359-66. doi: 10.1007/BF02890439.
To examine the significance of anti-catabolism in renal hypertrophy, cellular autophagy was investigated by electron microscopic morphometry in proximal tubular cells (PTCs) of the outer cortex of the rat kidney after the induction of diabetes mellitus by streptozotocin (STZ) and after unilateral nephrectomy. Adult male Sprague-Dawley rats were divided into three groups and killed by retrograde perfusion fixation, 1, 2 and 3 days after the induction of diabetes (group D; n = 24), after unilateral nephrectomy (group N; n = 24) and after combined treatment (group DN; n = 24). Untreated, age-matched litter mates served as controls (group C; n = 24). By comparison with these controls, the left kidney to initial body weight ratio was increased by 8, 23, and 15% in group D animals, by 8, 23, and 24% in group N animals, and by 10, 21, and 25% in group DN animals at the first, second and third day, respectively. Quantitative evaluation of large test areas showed that the volume and numerical densities of autophagic vacuoles (AVs) in PTCs were significantly lower in these hypertrophed kidneys than in the controls. The average reduction in AV volume density was about 65% in group D animals, about 50% in group N animals and about 75% in group DN animals. These data show that autophagic degradation of cytoplasmic components in PTCs is inhibited in renal hypertrophy independently of the growth stimulus, i.e. uninephrectomy or diabetes. Since insulin per se inhibits cellular autophagy in PTCs, the expected effect of insulin dificiency seems to be counteracted by as yet undefined stimuli that may be related to metabolic work load.
为了研究抗分解代谢在肾肥大中的意义，通过电子显微镜形态计量学对链脲佐菌素（STZ）诱导糖尿病后及单侧肾切除术后大鼠肾外皮质近端肾小管细胞（PTCs）中的细胞自噬进行了研究。成年雄性Sprague-Dawley大鼠分为三组，分别在糖尿病诱导后1天、2天和3天（D组；n = 24）、单侧肾切除术后（N组；n = 24）以及联合治疗后（DN组；n = 24）通过逆行灌注固定处死。未经处理、年龄匹配的同窝仔鼠作为对照（C组；n = 24）。与这些对照相比，D组动物在第1天、第2天和第3天左肾与初始体重之比分别增加了8%、23%和15%，N组动物分别增加了8%、23%和24%，DN组动物分别增加了10%、21%和25%。对大测试区域的定量评估显示，这些肥大肾脏中PTCs自噬泡（AVs）的体积和数量密度明显低于对照组。D组动物AV体积密度平均降低约65%，N组动物约50%，DN组动物约75%。这些数据表明，PTCs中细胞质成分的自噬降解在肾肥大中受到抑制，与生长刺激无关，即与单侧肾切除或糖尿病无关。由于胰岛素本身可抑制PTCs中的细胞自噬，胰岛素缺乏的预期效应似乎被可能与代谢工作负荷相关的尚未明确的刺激所抵消。
