Effects of exendin-4 on the intrarenal renin-angiotensin system and interstitial fibrosis in unilateral ureteral obstruction mice: Exendin-4 and unilateral ureteral obstruction.
Effects of exendin-4 on the intrarenal renin-angiotensin system and interstitial fibrosis in unilateral ureteral obstruction mice: Exendin-4 and unilateral ureteral obstruction.
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Exendin-4对单侧输尿管梗阻小鼠肾内肾素-血管紧张素系统和间质纤维化的影响：Exendin-4和单侧输尿管梗阻。
DOI：
10.1177/1470320316677918
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Le Y;Zheng Z;Xue J;Cheng M;Guan M;Xue Y
本研究旨在探讨exendin-4对单侧输尿管梗阻（UUO）小鼠肾脏的保护作用及其可能机制。雄性Balbc小鼠进行假手术或UUO手术，然后分别接受腹膜内注射媒介物或exendin-4。14 d后处死小鼠，取左肾行组织学、免疫组化、Western blot、实时定量逆转录聚合酶链反应、放射免疫分析和酶联免疫吸附试验。与假手术组相比，接受UUO手术的小鼠发生了更严重的肾小管损伤和间质纤维化，以及纤维连接蛋白（FN）、胶原-1（Col-1）和α-平滑肌肌动蛋白（α-SMA）的更高表达。血管紧张素转换酶（ACE）表达增高，血管紧张素转换酶2（ACE 2）表达降低;肾内血管紧张素II（Ang II）表达增高，血管紧张素-（1-7）表达降低;转化生长因子β1（TGF-β1）表达增高，Smad 3磷酸化（p-Smad 3）表达增高。令人印象深刻的是，这些病理变化在用exendin-4处理的UUO小鼠组中显著减弱。我们的研究首次表明exendin-4在UUO实验模型中发挥肾脏保护作用，部分通过调节肾内肾素-血管紧张素系统的平衡，然后抑制Ang II介导的TGF-β1/Smad 3信号通路。
The objective of this article is to investigate the renoprotecive effects of exendin-4 in a mouse model of unilateral ureteral obstruction (UUO) and explore the putative mechanisms. Male Balbc mice underwent sham operation or UUO surgery, and then received intraperitoneal injection of vehicle or exendin-4, respectively. After 14 days, mice were sacrificed and the left kidneys were collected and analyzed by histology, immunohistochemistry, Western blot, quantitative real-time reverse transcription polymerase chain reaction, radioimmunoassay and enzyme-linked immunosorbent assay. As compared to the sham group, mice that underwent UUO surgery developed more severe tubular injury and interstitial fibrosis, as well as higher expression of fibronectin (FN), collagen-1 (Col-1) and α-smooth muscle actin (α-SMA). Also, we observed higher expression of angiotensin-converting enzyme (ACE) while lower expression of angiotensin-converting enzyme 2 (ACE2), higher levels of intrarenal angiotensin II (Ang II) while lower levels of intrarenal angiotensin-(1–7), and higher expression of transforming growth factor β1 (TGF-β1) and phosphorylation of Smad3 (p-Smad3) in the obstructed kidneys. Impressively, these pathologic changes were significantly attenuated in the mice group of UUO treated with exendin-4. Our present study indicates for the first time that exendin-4 exerts renoprotective effects in an experimental model of UUO, partly through regulating the balance of the intrarenal renin-angiotensin system and then inhibiting the Ang II-mediated TGF-β1/Smad3 signaling pathway.
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影响因子：
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DOI：
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发表时间：
2011-10-18
期刊：
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影响因子：
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