Exploring protective mechanism of resveratrol on rat kidney in gouty nephropathy model based on NF-κB/NLRP3/Caspase-1 signaling axis
Objective Exploring the protective mechanism of resveratrol on rat kidney in gouty nephropathy model based on NF-κB/NLRP 3/Caspase-l signaling axis.Method Sixty male SD rats were randomly divided into control group,model group,colchicine(positive control,0.03 mg·kg-1)group,and resveratrol high,medium,and low dose(1 000,500,250 mg·kg-1)group.The rats were administered ig for seven consecutive days.During the administration process,except for the control group,the other groups were prepared with potassium oxazinate combined with sodium urate to create a rat model of gouty nephropathy.Level of interleukin(IL)-1β,IL-18,uric acid,creatinine(SCr),urea nitrogen(BUN)in serum,and tumor necrosis factor-α(TNF-α),monocyte chemotactic protein-1(MCP-1)and cyclooxygenase-2(COX-2)levels in renal tissue homogenate were detected by ELISA method.The morphological changes of kidney tissues were observed by HE and Masson staining.The glomerular injury in rat renal tissue was detected by PAS staining.The DNA damage in kidney tissue cells was observed by TUNEL.The expression levels of NF-κB,NLRP3, Caspase-1 mRNA and protein in kidney tissues were detected by qRT-PCR and immunohistochemistry. Finally, molecular docking technology was used to study the combination between resveratrol and NF-κB, NLRP3, Caspase-1. Result Compared with model group, the levels of IL-1β, IL-18, SCr, and BUN in the serum and and TNF-α, MCP-1 and COX-2 in renal of rats treated with colchicine and resveratro were significantly reduced (P ＜ 0.01). While uric acid in the high-dose group of resveratrol, and BUN in medium and high dose group showed a significant decrease (P ＜ 0.05). Each dose group of resveratrol reduced the collagen fibrosis area, glomerular positivity rate, and TUNEL staining positivity rate of renal tissue cells to varying degrees, slowing down pathological damage, and the high-dose group had the most significant effect among them (P ＜ 0.05). qRT-PCR and immunohistochemistry results showed that all treatment groups of resveratrol inhibited NF-κB, NLRP3, and Caspase-1 mRNA and protein in renal tissue cells, with the high-dose group having the most significant effect (P ＜ 0.05). The molecular docking results further indicate that resveratrol interacts with NF- κB. The binding state of NLRP3 and Caspase-1 is good, indicating that resveratrol has an effect on NF-κB. NLRP3 and Caspase-1 have good targeted regulatory effects. The molecular docking results further indicated that, resveratrol binds well to NF- κB, NLRP3, and Caspase-1, resveratrol showed good targeted regulation of NF-κB,NLRP3 and Caspase-1. Conclusion The renal protective effect of resveratrol in GN model of gouty arthritis with hyperuricemia is related to the inhibition of inflammatory factor secretion. Its anti-inflammatory mechanism may be through the inhibition of NF-κB signaling pathway, and then NLRP3 activation to block Caspase-1 recruitment of IL-1 IL-1 and IL-18, reduce the secretion of inflammatory factors such as IL-1β and IL-18, and curb the occurrence of cell pyroptosis in the initial stage of programmed renal cell death, thus reversing the inflammatory injury of renal tissue in GN.
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