Zhou Yun, Takahashi Go, Shinagawa Toshihito, Okuhara Toshini, Yonamine Kyoko, Aida Yoshio, Tadokoro Mamoru
Department of Urology, St Marianna University School of Medicine, Kawasaki, Japan.
Int J Urol. 2002 Sep;9(9):491-500. doi: 10.1046/j.1442-2042.2002.00507.x.
Most of our knowledge concerning renal obstruction has been derived from experimental animal models, and it is not yet well defined in spontaneous hydronephrosis. The aim of our study is to evaluate the roles of transforming growth factor-beta1 (TGF-beta1) and apoptosis in congenital hydronephrotic kidneys in comparison with experimental models.
We made histological studies on kidneys from 6-week-old Wistar-Imamichi rats with congenital unilateral hydronephrosis as well as surgical models of complete or partial unilateral ureteral obstruction. The severity of hydronephrotic kidneys was evaluated on routine hematoxylin and eosin (H&E) stained sections, and the tubulointerstitial fibrosis analyzed morphometrically on Masson's trichrome stained sections. Renal tubular atrophy was assessed on periodic acid Schiff (PAS) stained sections, and tubular cell apoptosis assessed with TUNEL technique. The renal TGF-beta1 level was determined by a sandwich enzyme-linked immunosorbent assay (ELISA).
We observed a significant loss of kidney weight with profound compensatory growth of the contralateral kidney in rats with congenital hydronephrosis. Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, renal parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. The renal TGF-beta1 level was markedly elevated in hydronephrotic kidneys as compared with normal controls (326.01 +/- 30.64 pg/mg protein vs 227.81 +/- 11.07 pg/mg protein, P < 0.01). The tubular apoptotic score in hydronephrotic kidneys was also significantly higher than normal controls (2.17 +/- 0.50/HPF [high power field]vs 0.14 +/- 0.04/HPF, P < 0.01). The increased TGF-beta1 and apoptotic status paralleled the histological changes of tubulointerstitial fibrosis and tubular atrophy. Similar findings were also obtained in experimental obstructive models.
In comparison with surgical models of partial and complete ureteral obstruction, our data provide solid morphological and molecular evidences of renal obstruction in rats with congenital hydronephrosis.
我们关于肾梗阻的大部分知识来源于实验动物模型，而在自发性肾积水方面尚未明确界定。本研究的目的是比较先天性肾积水肾脏与实验模型中转化生长因子-β1（TGF-β1）和细胞凋亡的作用。
我们对6周龄先天性单侧肾积水的Wistar-Imamichi大鼠以及完全或部分单侧输尿管梗阻的手术模型的肾脏进行了组织学研究。在常规苏木精和伊红（H&E）染色切片上评估肾积水肾脏的严重程度，并在Masson三色染色切片上进行形态计量分析肾小管间质纤维化。在过碘酸希夫（PAS）染色切片上评估肾小管萎缩，并用TUNEL技术评估肾小管细胞凋亡。通过夹心酶联免疫吸附测定（ELISA）测定肾脏TGF-β1水平。
我们观察到先天性肾积水大鼠的肾脏重量显著减轻，对侧肾脏出现明显的代偿性生长。大多数肾积水肾脏明显增大，伴有集合系统扩张、肾实质变薄、肾小管萎缩、间质浸润和纤维化。与正常对照组相比，肾积水肾脏中的肾TGF-β1水平显著升高（326.01±30.64 pg/mg蛋白对227.81±11.07 pg/mg蛋白，P<0.01）。肾积水肾脏中的肾小管凋亡评分也显著高于正常对照组（2.17±0.50/高倍视野[HPF]对0.14±0.04/HPF，P<0.01）。TGF-β1增加和凋亡状态与肾小管间质纤维化和肾小管萎缩的组织学变化平行。在实验性梗阻模型中也获得了类似的结果。
与部分和完全输尿管梗阻的手术模型相比，我们的数据为先天性肾积水大鼠的肾梗阻提供了可靠的形态学和分子证据。
