Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, China.
Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China.
Nephron. 2019;142(3):233-242. doi: 10.1159/000497489. Epub 2019 Feb 21.
The progression of chronic renal failure in patients with unilateral renal injury is associated with loss of function in the contralateral kidney, but the molecular mechanism remains unclear. The activation of mineralocorticoid receptor (MR) in the kidney contributes to renal cell damage, leading to apoptosis, pyroptosis, and necrosis. Pyroptosis is a programmed cell death induced by caspase-1, which is usually activated by nod-like receptor pyrin-containing 3 (NLRP3) inflammasomes. Our study aimed to investigate the effects of eplerenone (EPL) on cell pyroptosis in the contralateral kidneys of unilateral ureteral obstruction (UUO) rats.
Sprague-Dawley rats were randomly divided into 3 groups: sham group, UUO group (10 days of left ureter ligation), and UUO treated with EPL (UUO + EPL) group. The contralateral kidneys of all rats were collected for studies.
We observed evidently increased number of pyroptosis cells in the contralateral kidneys of UUO rats compared to those from Sham rats. The expression of NLRP3, caspase-1, interleukin-1β, serum and glucocorticoid-inducible protein kinase-1, and nuclear factor kappa B were also upregulated in the contralateral kidneys of UUO rats compared to Sham kidneys, and these effects were reduced by MR blocker EPL.
Our data suggest that the activation of MR is involved in NLRP3/caspase-1 pathway-induced cell pyroptosis in the contralateral kidney of UUO model.
单侧肾损伤患者慢性肾衰竭的进展与对侧肾脏功能丧失有关，但分子机制尚不清楚。肾脏中醛固酮受体（MR）的激活导致肾细胞损伤，引发细胞凋亡、细胞焦亡和细胞坏死。细胞焦亡是一种由半胱氨酸天冬氨酸蛋白酶-1（caspase-1）诱导的程序性细胞死亡，通常由核苷酸结合寡聚化结构域样受体含pyrin 结构域 3（NLRP3）炎性小体激活。本研究旨在探讨依普利酮（EPL）对单侧输尿管梗阻（UUO）大鼠对侧肾脏细胞焦亡的影响。
将 Sprague-Dawley 大鼠随机分为 3 组：假手术组、UUO 组（左输尿管结扎 10 天）和 UUO 加 EPL 组（UUO+EPL 组）。所有大鼠的对侧肾脏均用于研究。
与 Sham 组大鼠相比，UUO 组大鼠对侧肾脏中发生细胞焦亡的细胞数量明显增加。与 Sham 肾脏相比，UUO 大鼠对侧肾脏中 NLRP3、caspase-1、白细胞介素-1β、血清和糖皮质激素诱导的蛋白激酶-1 和核因子κB 的表达也上调，这些作用被 MR 阻滞剂 EPL 减弱。
我们的数据表明，MR 的激活参与了 NLRP3/caspase-1 通路诱导的 UUO 模型对侧肾脏细胞焦亡。
