Inhibition of IL-1β by Aliskiren Improved Renal AQP2 Expression and Urinary Concentration Defect in Ureteral Obstruction and Release
Inhibition of IL-1β by Aliskiren Improved Renal AQP2 Expression and Urinary Concentration Defect in Ureteral Obstruction and Release
复制标题
阿利吉仑抑制 IL-1β 可改善输尿管梗阻和松解中的肾 AQP2 表达和尿浓缩缺陷
DOI：
10.3389/fphys.2019.01157
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发表时间：
2019-09-13
影响因子：
4
通讯作者：
Li, Chunling
中科院分区：
文献类型：
--
作者：
Hu, Shan;Xie, Haixia;Li, Chunling
我们以前证明，输尿管梗阻与尿浓缩缺陷和肾水通道蛋白（AQP）表达减少有关，其中肾素-血管紧张素系统（RAS）可能起着重要作用。本研究的目的是检查是否肾素抑制剂阿利吉仑可以防止水通道蛋白表达的减少，并提高尿浓缩能力，在小鼠双侧输尿管梗阻（BUO）和BUO释放。BUO进行24小时，BUO释放进行1天（B-R1 D）或3天（B-R3 D），有或没有阿利吉仑治疗。阿利吉仑预防B-R3 D诱导的多尿和降低尿渗透压。在BUO和BUO释放的小鼠中，阿利吉仑减弱了梗阻肾脏中AQP 2蛋白和mRNA表达的降低。B-R3 D增加了阻塞肾脏中NLRP 3炎性体组分ASC、半胱天冬酶-1和白细胞介素-1 β的蛋白表达，阿利吉仑显著阻止了这一点。此外，NF-κ B B抑制剂Bay 11-7082阻断了血管紧张素II处理的原代培养大鼠内髓集合管细胞中NLRP 3炎性体的激活并减弱了AQP 2蛋白表达的降低。这些结果表明，肾素抑制剂阿利吉仑增加水通道AQP 2的表达，至少部分通过抑制NLRP 3炎性小体激活在阻塞的肾脏与BUO和BUO释放的小鼠。
We previously demonstrated that ureteral obstruction is associated with a urinary concentrating defect and reduced expression of renal aquaporins (AQPs), in which the renin-angiotensin system (RAS) may play an important role. The aims of the present study were to examine whether the renin inhibitor aliskiren could prevent the reduction in AQP expression and improve the urinary concentrating capacity in mice with bilateral ureteral obstruction (BUO) and BUO release. BUO was performed for 24 h, and BUO release was performed for 1 (B-R1D) or 3 days (B-R3D) with or without aliskiren treatment. Aliskiren prevented polyuria and decreased urine osmolality induced by B-R3D. In mice with BUO and BUO release, aliskiren attenuated the reduction in AQP2 protein and mRNA expression in the obstructed kidneys. B-R3D increased the protein expression of NLRP3 inflammasome components ASC, caspase-1, and interleukin-1 beta in the obstructed kidneys, which was markedly prevented by aliskiren. Moreover, the NF-kappa B inhibitor Bay 11-7082 blocked NLRP3 inflammasome activation and attenuated the decrease in AQP2 protein expression in primary cultured rat inner medullary collecting duct cells treated with angiotensin II. These results indicate that the renin inhibitor aliskiren increases water channel AQP2 expression at least partially by suppressing NLRP3 inflammasome activation in the obstructed kidneys of mice with BUO and BUO release.