Division of Pathology, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, 210-9501, Japan.
Laboratory of Animal Pathology, Faculty of Animal Health Technology, Yamazaki University of Animal Health Technology, 4-7-2 Minami Osawa, Hachioji, Tokyo 192-0364, Japan.
Toxicol Sci. 2018 Oct 1;165(2):420-430. doi: 10.1093/toxsci/kfy151.
Osmotic nephrosis, a disease caused by intravenous infusion of various fluids such as hypertonic sucrose and isotonic polysaccharide-based plasma volume expanders, exhibits specific histopathological features, including vacuolated and swollen proximal tubules, ie, "clear tubules". Pre-existing kidney injury exacerbates this condition, resulting in major clinical problems. However, the underlying mechanisms are unclear. Animal models often yield results that are directly translatable to humans. Therefore, in this study, we performed detailed histopathological analyses of the formation of clear tubules in rats treated with gentamicin or ischemia/reperfusion (IR) operation followed by dextran administration. The results showed that clear tubules may originate from regenerative tubules. Additionally, we classified regenerative tubules into 3 categories based on their development, with a particular focus on the middle and late stages. Comprehensive microarray and real-time polymerase chain reaction analyses of mRNA extracted from regenerative tubules at each stage using laser microdissection revealed that regenerative tubules in the middle stage showed an imbalance between dextran absorption and metabolism, resulting in accumulation of dextran, particularly in the cytoplasm of the tubules. Overall, our findings demonstrated that clear tubules originated from regenerated tubules and that tubules at the middle stage became clear tubules because of an imbalance during their development. This could explain why osmotic nephrosis is exacerbated in the presence of kidney lesions.
渗透性肾病是由静脉输注各种液体引起的疾病，如高渗蔗糖和等渗多糖类血浆容量扩充剂，表现出特定的组织病理学特征，包括空泡和肿胀的近端肾小管，即“透明小管”。预先存在的肾脏损伤会加重这种情况，导致主要的临床问题。然而，其潜在机制尚不清楚。动物模型通常会产生直接适用于人类的结果。因此，在这项研究中，我们对氨基糖苷类药物或缺血/再灌注（IR）操作后给予右旋糖酐治疗的大鼠中透明小管形成进行了详细的组织病理学分析。结果表明，透明小管可能起源于再生小管。此外，我们根据其发育将再生小管分为 3 类，特别关注中晚期。使用激光微切割从每个阶段的再生小管中提取 mRNA 进行综合微阵列和实时聚合酶链反应分析表明，中期的再生小管在右旋糖酐吸收和代谢之间出现失衡，导致右旋糖酐积累，特别是在小管的细胞质中。总的来说，我们的研究结果表明，透明小管起源于再生小管，而中期的小管成为透明小管是由于其发育过程中的不平衡。这可以解释为什么在存在肾脏病变的情况下渗透性肾病会加重。
