Abstract
BackgroundYi Qi Qing Re Gao (YQQRG) formula is a traditional Chinese herbal medicine used to treat chronic nephritis. This study was designed to evaluate the underlying mechanism in the use of YQQRG formula to treat nephrosis induced by puromycin aminonucleoside (PAN).MethodsThirty-six male Wistar rats were randomly divided into 3 groups of 12 rats each: a sham group, a vehicle-treated PAN model group (PAN), and a group treated with YQQRG (PAN + YQQRG). The PAN model was established by a single intravenous injection of PAN at a dose of 40 mg/kg body weight; rats in the sham group received the same volume of saline. Twenty-four hour urinary protein was measured 0, 3, 5, 10, and 15 days after the injection. The rats were sacrificed on day 10 and day 15 and the serum lipid profile examined. The renal cortex of each rat was stained with periodic acid–Schiff reagent and the pathologic alterations and ultrastructural changes were examined by transmission electron microscopy. In situ cell apoptosis was detected by a terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL) assay. Transcriptive levels of inflammatory markers and molecules associated with apoptosis were detected by a real-time polymerase chain reaction and expression of proteins was examined by either immunohistochemistry or Western blot analysis.ResultsYQQRG significantly decreased urinary protein level, and lowered serum lipid level. YQQRG also attenuated histologic lesions in the rat kidneys. Activation of inflammatory markers was largely restored by the administration of YQQRG. TUNEL assay showed that YQQRG decreased the number of apoptotic cells. Both mRNA and protein levels of caspase-3 were significantly reduced in the group treated with YQQRG, whereas expression of the Bcl-2 protein increased in the YQQRG group.ConclusionsYQQRG alleviated kidney injury in PAN-treated rats, possibly through anti-inflammatory and anti-apoptotic effects.
Highlights
Yi Qi Qing Re Gao (YQQRG) formula is a traditional Chinese herbal medicine used to treat chronic nephritis
Proteinuria level in the puromycin aminonucleoside (PAN) group was increased to 110.4 mg/24 h five days after the injection of PAN (P < 0.01)
Proteinuria level in the PAN group peaked at 338.2 mg/24 h on day 10 (P < 0.01) and decreased to 226.84 mg/24 h a day 15 (P < 0.01), whereas Proteinuria level in the sham group remained unchanged
Summary
Yi Qi Qing Re Gao (YQQRG) formula is a traditional Chinese herbal medicine used to treat chronic nephritis. This study was designed to evaluate the underlying mechanism in the use of YQQRG formula to treat nephrosis induced by puromycin aminonucleoside (PAN). Inflammation and apoptosis are typical pathological features shared by a variety of kidney diseases, such as glomerulosclerosis and tubulointerstitial fibrosis, which consequentially induce renal failure. Prevention and treatment of renal inflammation or apoptosis may be a key issue in treating kidney disease. Chemokines or adhesion molecules secreted by resident renal cells attract circulating inflammatory cells and induce infiltration of the inflammatory cells. Activated inflammatory cells, such as macrophages and neutrophils, are responsible for the production of various proinflammatory mediators. Various macrophage inhibition strategies have been used to successfully treat kidney diseases in animal models [3]. Monocyte chemoattractant protein (MCP-1), which triggers macrophage recruitment, has been found to be secreted by tubular epithelial cells in both patients with proteinuria and in proteinuric animal models
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