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.
Highlights
In the clinic, obstructive nephropathy has emerged as a major cause of end-stage renal diseases (ESRDs), especially in the countryside of China [1, 2]
F4/80 is the marker of rat macrophages which have classically been recognised as an active player in progressive renal scarring. e results showed that there were no changes on glomeruli from the sham group, and the glomerular structures were well preserved with a few inflammatory cells, and little collagen deposition was observed in the contralateral glomeruli. ere was a significant increase in macrophage infiltration into the contralateral unobstructed kidney (CK) compared with the sham after 10 days of ureteral obstruction (UUO), and it was ameliorated in the eplerenone group and Huoxue Jiedu Huayu Recipe (HJHR) group (Figure 1)
Our previous study found that cell pyroptosis in contralateral kidneys of rat with UUO is associated with the mineralocorticoid receptor (MR)/serum- and glucocorticoid-inducible protein kinase-1 (SGK-1) pathway [3]
Summary
Obstructive nephropathy has emerged as a major cause of end-stage renal diseases (ESRDs), especially in the countryside of China [1, 2]. Our previous studies have demonstrated that activated mineralocorticoid receptor (MR) in the contralateral unobstructed kidney (CK) of UUO plays an important role in the progression of renal interstitial fibrosis with the serum- and glucocorticoid-inducible protein kinase-1 (SGK-1) pathway [3]. Glomerular inflammation preceding interstitial fibrosis is a major process involved in the progression of glomerulosclerosis [4], and partial renal function loss on the CK accelerates progression of renal failure. Increasing evidence demonstrated that inflammation is attributable to the development and progression of kidney injury [4, 5]. We demonstrated that UUO-induced contralateral glomerular injury was characterized by mesangial cell pyroptosis. We observed that the UUO-induced contralateral glomerular injury was prevented by treatment with Huoxue Jiedu Huayu Recipe (HJHR) and eplerenone.
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