Uninephrectomy induces progressive glomerulosclerosis and apoptosis in anti-Thy1 glomerulonephritis
Uninephrectomy induces progressive glomerulosclerosis and apoptosis in anti-Thy1 glomerulonephritis
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DOI：
10.1111/j.1440-1827.2005.01781.x
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发表时间：
2005-01-01
影响因子：
2.2
通讯作者：
Suzuki, H
中科院分区：
文献类型：
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作者：
Sakai, N;Iseki, K;Suzuki, H
在大鼠中施用抗 Thy1 抗体会诱导可逆性肾小球肾炎，类似于人类系膜溶解症和系膜增生性疾病。本研究的目的是设计一个不可逆肾小球硬化模型，使用单肾切除后注射抗Thy1抗体，并对其进行检查，重点关注进行性硬化变化过程中的细胞凋亡。 Wistar大鼠被分为三组：单肾组（第一组和第三组）和双肾组（第二组）。所有组在第0天注射抗Thy1抗体(OX-7)，并且组I和III在第-6天不进行肾切除。仅第III组大鼠给予与第I组和第II组相比一半剂量的OX-7。第7、14、30天处死大鼠进行组织学检查。第14、30天，Ⅰ组出现进展性肾小球病变，如肾小球与鲍曼氏囊粘连、新月体形成、毛细血管簇塌陷等。Ⅰ组和Ⅲ组病理结果无显着差异。第 7 天和第 14 天时，与第 II 组相比，第 I 组的肾小球末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记阳性细胞数量显着增多。此外，第 7 天和第 14 天时，与第 II 组相比，第 I 组的肾小球表达转化生长因子-β、硫酸乙酰肝素蛋白聚糖和硫酸软骨素蛋白聚糖显着增加。通过在单侧肾切除术后单次注射抗 Thy1 抗体在大鼠中诱导。提示细胞凋亡和细胞外基质积累在肾小球硬化的发生发展中起重要作用。
Administration of the anti-Thy1 antibody in rats induces reversible glomerulonephritis resembling human mesangiolytic and mesangioproliferative diseases. The purpose of the present study was to design a model of irreversible glomerulosclerosis, using the anti-Thy1 antibody injection after uninephrectomy, and examine it, focusing on apoptosis in the process of progressive sclerotic changes. Wistar rats were divided into three groups: one-kidney groups (group I and III) and a two-kidney group (group II). All groups were injected with the anti-Thy1 antibody (OX-7) at day 0, and group I and III were uninephrectomized at day -6. Only group III rats were given a half dose of OX-7 as compared with group I and II. Rats were killed for histological examinations at days 7, 14 and 30. In group I, progressive glomerular lesions, such as glomerular adhesion to Bowman's capsule, crescent formation, and collapse of capillary tufts were observed at days 14 and 30. No significant differences were observed in the pathological findings between group I and III. There was a significantly higher number of glomerular terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells in group I as compared to group II at days 7 and 14. Moreover, the glomerular expression of transforming growth factor-beta, heparan sulfate proteoglycan and chondroitin sulfate proteoglycan significantly increased in group I as compared to group II at days 7 and 14. Progressive glomerulosclerosis can be induced in the rat by a single injection of the anti-Thy1 antibody after unilateral nephrectomy. It is suggested that apoptosis and extracellular matrix accumulation play an important role in the development of glomerulosclerosis.