TGF-β1 production in radiation nephropathy:: role of angiotensin II
TGF-β1 production in radiation nephropathy:: role of angiotensin II
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DOI：
10.1080/095530099140401
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发表时间：
1999-04-01
影响因子：
2.6
通讯作者：
Lianos, EA
中科院分区：
文献类型：
--
作者：
Datta, PK;Moulder, JE;Lianos, EA
目的：血管紧张素Ⅱ受体拮抗剂对放射性肾病的预防有一定的作用。研究旨在确定TGF-β 1（一种纤维化细胞因子）是否在介导AII拮抗作用的保护作用中发挥作用。这些研究探索了照射肾脏中肾小球TGF-β 1产生的时间过程，以及AII是否介导从照射大鼠分离的肾小球中TGF-β 1的产生。大鼠分5次接受20戈伊双侧肾照射，并随机接受AII 1型受体拮抗剂（L-158，809），或不处理。药物治疗开始前9天的照射，并持续的研究期间。结果：肾功能分析显示，照射后37天和63天，分别在尿蛋白尿和血尿素氮显着增加。通过定量夹心酶免疫分析技术估计肾小球TGF-β 1水平显示，在照射后50天和63天，潜伏性但非活性TGF-β 1水平显著增加。在用ATI受体拮抗剂治疗的动物中，TGF-β 1的升高被完全消除。结论：这些研究表明，在放射性肾病过程中肾小球TGF-β 1的产生增加，并且AII介导了这种TGF-β 1的诱导。
Purpose: Angiotensin II receptor antagonists are effective in the prophylaxis of radiation nephropathy. Studies were designed to determine whether TGF-beta 1, a fibrogenic cytokine, plays a role in mediating the protective effect of AII antagonism. These studies explored the time-course of glomerular TGF-beta 1 production in the irradiated kidney, and whether AII mediates TGF-beta 1 production in glomeruli isolated from irradiated rats.Materials and methods: Rats received 20 Gy of bilateral renal irradiation in five fractions and were randomized to receive an AII type 1 receptor antagonist (L-158,809) at 20 mg/l in their drinking water, or no treatment. Drug therapy began 9 days prior to irradiation and continued for the duration of the study.Results: Analysis of renal function showed a significant increase in urinary proteinuria and blood urea nitrogen by 37 days and 63 days after irradiation, respectively. Estimation of glomerular TGF-beta 1 levels by quantitative sandwich enzyme immunoassay technique revealed a significant increase in latent but not active TGF-beta 1 levels at 50 days and 63 days after irradiation. In animals treated with the ATI receptor antagonist, there was a complete elimination in the rise of TGF-beta 1.Conclusions: These studies demonstrate that glomerular TGF-beta 1 production is elevated in the course of radiation nephropathy, and that AII mediates this induction of TGF-beta 1.