Abstract
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). This study aimed to characterize Danggui Buxue Tang (DBT) renoprotection and relationship with NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome expression in rats with unilateral ureteral obstruction (UUO). Sprague-Dawley rats were subjected to UUO and randomly assigned to untreated UUO, enalapril-treated (10 mg/kg/day), and DBT-treated (9 g/kg/day) groups. Sham-operated rats served as controls, with 8 rats in each group. All rats were sacrificed for blood and renal specimen collection at 14 days after UUO. Untreated UUO rats exhibited azotemia, intense tubulointerstitial collagen deposition, upregulations of tubulointerstitial injury index, augmentation levels of collagen I (Col I), α-smooth muscle actin (α-SMA), NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase-1, caspase-1, IL-1β, and pro-IL-1β. DBT treatment significantly attenuated interstitial collagen deposition and tubulointerstitial injury, lowering Col I and α-SMA levels. Synchronous expressions of NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1β, and IL-1β decreased in renal tissue. In comparison to enalapril, DBT significantly reduced tubulointerstitial injury, interstitial collagen deposition, and expressions of Col I and IL-1β. Thus, DBT offers renoprotection in UUO rats, which was associated with suppressing NLRP3 inflammasome expression and following reduction of the secretion of cytokine IL-1β. The mechanisms of multitargets of traditional Chinese medicine can be better used for antifibrotic treatment.
Highlights
Fibrosis is the common final manifestation of progressive diseases in kidney, lung, heart, and liver that leads to end-stage organ diseases
There were no significant differences in the levels of Serum creatinine (Scr) (p = 0.972) and blood urea nitrogen (BUN) (p = 0.868) between enalapril and Danggui Buxue Tang (DBT) groups, but DBT possessed a better renal protective effect than enalapril on ureteral obstruction (UUO) rats on numerical level
Renal tubular epithelial cells injuries were due to a variety of insults, including ischemia, obstruction, and immune-mediated mechanisms [33], which can result in the release of endogenous cellular components and activate the NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome in rats with UUO [34]
Summary
Fibrosis is the common final manifestation of progressive diseases in kidney, lung, heart, and liver that leads to end-stage organ diseases. With the increasing patients and limited therapeutic options, chronic renal disease (CKD) and tubulonterstitial fibrosis (TIF) are becoming an important cause of morbidity and mortality worldwide. Inflammation significantly contributes to the progression of chronic kidney disease (CKD) and TIF [1,2,3,4]. Inflammasomes are multiprotein cytoplasmic complexes that serve as pattern recognition receptors and regulate proinflammatory cytokine Interleukin-1β (IL-1β) production [5]. NOD-like receptors family pyrin domain-containing 3 (NLRP3), the most characterized inflammasome, forms complexes comprised of adaptor proteins such as the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the serine protease caspase-1 (Casp). IL-1β (p17) is synthesized as an inactive precursor molecule (pro-IL-1β, p35) by cells of the innate immune system and is a proinflammatory cytokine produced by activated macrophages and BioMed Research International monocytes. Infiltrating macrophages are the major source of IL-1β in renal disease
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