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[间质性肾纤维化的发病机制。单侧输尿管梗阻大鼠模型的研究]

[Pathogenesis of interstitial kidney fibrosis. Studies in the rat model of unilateral ureteral obstruction].

作者信息

Sommer M, Fünfstück R

机构信息

Klinik für Innere Medizin, Friedrich-Schiller-Universität Jena.

出版信息

Med Klin (Munich). 1997 Oct 15;92(10):582-8. doi: 10.1007/BF03044783.

DOI:10.1007/BF03044783
PMID:9446005
Abstract

BACKGROUND

The animal model of unilateral ureteral obstruction (UUO) of the rat is suitable to cause a renal interstitial fibrosis within a few weeks. Prior to the 10th day after UUO, no fibrotic changes were detectable in ureter-ligated kidneys, whereas after day 20 fibrosis was developing strongly.

METHOD

Using cell cultures it was examined whether any in vivo changes in proliferation and function of fibroblasts are also detectable in cell cultures and whether, due to their persistency, they are of fundamental importance for the development of renal interstitial fibrosis.

RESULTS

The comparison of the proliferation in cell cultures established 5 and 21 days after UUO showed that the cultures of the two experimental groups behave similarly. Consequently, the action of acute inflammatory processes on fibroblast proliferation without any existing fibrosis is comparable with that of pronounced fibrosis in the animal model. High concentrations of fetal calf serum in the culture medium cause a stimulation of the cell proliferation as well as a selection of mitotically active differentiation stages of fibroblasts.

CONCLUSION

Obviously, the loss of inhibition of the fibroblast proliferation under the conditions of cell culture causes similar changes to those effected by pathogenic mechanisms in the kidneys of rats with UUO. If the behaviour of fibroblasts in organs is to be assessed using results of cell culture experiments, the stimulating action of the culture conditions and the missing influence of other cells present in the tissue should be considered. These factors make the recognition of remaining differences between cells from normal and damaged kidneys more difficult under the conditions of primary cell cultures.

摘要

背景

大鼠单侧输尿管梗阻(UUO)动物模型适合在几周内引发肾间质纤维化。在UUO后第10天之前,输尿管结扎的肾脏中未检测到纤维化变化,而在第20天后纤维化发展强烈。

方法

使用细胞培养来检查成纤维细胞增殖和功能的任何体内变化在细胞培养中是否也可检测到,以及由于它们的持续性,它们对肾间质纤维化的发展是否至关重要。

结果

对UUO后5天和21天建立的细胞培养物中的增殖进行比较表明,两个实验组的培养物表现相似。因此,在没有任何现有纤维化的情况下急性炎症过程对成纤维细胞增殖的作用与动物模型中明显纤维化的作用相当。培养基中高浓度的胎牛血清会刺激细胞增殖,并选择成纤维细胞有丝分裂活跃的分化阶段。

结论

显然,在细胞培养条件下成纤维细胞增殖抑制的丧失会导致与UUO大鼠肾脏中致病机制所引起的变化相似的改变。如果要使用细胞培养实验的结果来评估成纤维细胞在器官中的行为,则应考虑培养条件的刺激作用以及组织中存在的其他细胞的缺失影响。在原代细胞培养条件下,这些因素使得识别正常肾脏和受损肾脏细胞之间的剩余差异更加困难。

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