Yuxuan Zhang1, Juan Hao1, Xuelian Ma1,2, Qiyue Zhao1, Xiaomeng Gao1, Xiangting Wang1,2, Qingyou Xu1,2,3. 1. Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, China. 2. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China. 3. Department of Internal Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
Abstract
OBJECTIVES: To observe the effects of the Huoxue Jiedu Huayu Recipe (HJHR) on pyroptosis of glomerular mesangial cells in the contralateral unobstructed kidney (CK) of unilateral ureteral obstruction (UUO) rats. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: sham group, UUO group (10 days of left ureter ligation), UUO treated with eplerenone (EPL) (UUO + EPL) group, and UUO treated with HJHR (UUO + HJHR) group. The CKs of all rats were collected for studies. RESULTS: Cell pyroptosis and macrophage infiltration was found in contralateral glomeruli, and nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) and interleukin (IL)-1β expression was upregulated in the CK of UUO rats. All of these changes were inhibited by HJHR and eplerenone. To determine how aldosterone (Aldo) activated the mineralocorticoid receptor (MR) and then induced mesangial cell pyroptosis with NLRP3-caspase-1-IL-1β pathway, human mesangial cells (HMCs) were treated with HJHR and eplerenone, which were examined to detect the expression of NLRP3 inflammasome-associated proteins following treatment with Aldo. CONCLUSION: These results suggest that HJHR and eplerenone suppressed HMC pyroptosis via the MR/NLRP3 pathway.
OBJECTIVES: To observe the effects of the Huoxue Jiedu Huayu Recipe (HJHR) on pyroptosis of glomerular mesangial cells in the contralateral unobstructed kidney (CK) of unilateral ureteral obstruction (UUO) rats. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: sham group, UUO group (10 days of left ureter ligation), UUO treated with eplerenone (EPL) (UUO + EPL) group, and UUO treated with HJHR (UUO + HJHR) group. The CKs of all rats were collected for studies. RESULTS: Cell pyroptosis and macrophage infiltration was found in contralateral glomeruli, and nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) and interleukin (IL)-1β expression was upregulated in the CK of UUO rats. All of these changes were inhibited by HJHR and eplerenone. To determine how aldosterone (Aldo) activated the mineralocorticoid receptor (MR) and then induced mesangial cell pyroptosis with NLRP3-caspase-1-IL-1β pathway, human mesangial cells (HMCs) were treated with HJHR and eplerenone, which were examined to detect the expression of NLRP3 inflammasome-associated proteins following treatment with Aldo. CONCLUSION: These results suggest that HJHR and eplerenone suppressed HMC pyroptosis via the MR/NLRP3 pathway.
Authors: Akosua Vilaysane; Justin Chun; Mark E Seamone; Wenjie Wang; Rick Chin; Simon Hirota; Yan Li; Sharon A Clark; Jurg Tschopp; Kiril Trpkov; Brenda R Hemmelgarn; Paul L Beck; Daniel A Muruve Journal: J Am Soc Nephrol Date: 2010-08-05 Impact factor: 10.121