Kida Y, Sato T
Department of Anatomy II, School of Dental Medicine, Tsurumi University, Yokohama, Japan.
Histol Histopathol. 2007 Mar;22(3):291-303. doi: 10.14670/HH-22.291.
The main focus of the present investigation is to examine obstructed kidneys due to unilateral ureteral obstruction (UUO) model in adult mice using segment-specific tubular marker and to confirm the detailed morphological evaluation of UUO that is a typical model for the tubulointerstitial fibrosis which is an endpoint outcome of chronic renal diseases. Adult mice were subjected to UUO, and kidneys were harvested 1, 3, 7 days after surgical operation. Expansion of interstitial space both in the cortex and the medulla was confirmed 3 days after UUO by HE- and azan-staining. Interstitial fibrosis developed especially around dilated tubules. Immunohistochemistry for segment-specific antibodies revealed that the proximal tubules and the descending limb of Henle's loop did not dilate until 7 days after UUO, whereas initial dilation of the ascending limb of Henle's loop appeared to occur one day after surgery. The segment from the distal tubules to the collecting ducts began dilating one day after surgery and afterward significantly dilated. The downstream segment of nephron was involved in dilating earlier than the upstream of nephron in obstructed kidney examined in the present study. Moreover, the tubules accompanying apoptosis of tubular epithelia significantly dilated compared with those without apoptotic tubular epithelia. From the above-mentioned findings, we conclude that tubular dilatation of distal segment (from the ascending limb of Henle's loop to the collecting ducts) of nephron develops tubular epithelial apoptosis caused by accumulated urine, which would link to tubular disappearance and its replacement with fibrous tissue in UUO kidney of adult mice.
本研究的主要重点是使用节段特异性肾小管标志物,在成年小鼠中研究单侧输尿管梗阻(UUO)模型所致的梗阻性肾脏,并对UUO进行详细的形态学评估,UUO是慢性肾脏疾病终末期结局肾小管间质纤维化的典型模型。成年小鼠接受UUO手术,术后1、3、7天摘取肾脏。通过苏木精-伊红(HE)染色和偶氮胭脂红染色证实,UUO术后3天皮质和髓质的间质间隙均扩大。间质纤维化尤其在扩张的肾小管周围发展。针对节段特异性抗体的免疫组织化学显示,近端小管和髓袢降支直到UUO术后7天才扩张,而髓袢升支在术后1天似乎就开始出现初始扩张。远曲小管至集合管节段在术后1天开始扩张,随后显著扩张。在本研究检测的梗阻性肾脏中,肾单位的下游节段比上游节段更早出现扩张。此外,伴有肾小管上皮细胞凋亡的肾小管与无凋亡肾小管上皮细胞的肾小管相比,显著扩张。根据上述发现,我们得出结论,肾单位远段(从髓袢升支到集合管)的肾小管扩张会导致因尿液积聚引起的肾小管上皮细胞凋亡,这可能与成年小鼠UUO肾脏中肾小管消失及其被纤维组织替代有关。