The Study On The Regulation Mechanism Of NLRP₃ Inflammasome Signaling Pathway In Gouty Nephropathy

BackgroundIn the state of long-term hyperuricemia,monosodium urate crystals can be deposited in the kidney,causing gouty nephropathy.It is believed that the activation of renin-angiotensin system,endothelial dysfunction and inflammatory damage play important roles in gouty nephropathy.It has started to reveal that inflammation has attracted more attention in gouty nephropathy in recent years.Peripheral blood monocytes involved in the body’s innate immunity,which caused inflammation by the pattern recognition receptor sensing danger signals.NOD-like receptor protein domain 3(NLRP3)is a kind of intracellular pattern recognition receptor,which is associated with ASC and caspase-1 to form NLRP3 inflammasome,inducing the secretion of inflammatory cytokines,playing an important role in inflammation.The present study aimed to investigate the expression levels of NLRP3 inflammasome and downstream inflammatory factors IL-1β/IL-18,revealing the mechanism of NLRP3 inflammasome signaling pathway in hyperuricemia and gouty nephropathy,through which provides a new theoretical basis and therapeutic target for the early prevention and treatment of gouty nephropathy.MethodsObject of Study:We recruited adult male patients between July 2016 and June 2017 in Affiliated Baoan Hospital of Shenzhen,Southern Medical University.These patients were divided into three groups of 15 patients each:the control group,hyperuricemia group and gouty nephropathy group.Detection Indicators:(1)General clinical indicators:blood creatinine,urea nitrogen,blood uric acid,urine leukocyte,urine erythrocyte and urine protein;(2)We isolated the peripheral blood monocytes by magnetic beads negative selection,then identified and counted;(3)We detected the expression of NLRP3,ASC and caspase-1 mRNA by real-time quantitative PCR in peripheral blood monocytes;(4)We detected the expression of NLRP3,ASC and caspase-1 protein by Western blot in peripheral blood monocytes;(5)We detected the expression of IL-1β and IL-18 in plasma.ResultsCompared with the control group,blood creatinine,urea nitrogen and uric acid were significantly elevated in hyperuricemia group(P<0.05).The expression of NLRP3 mRNA in peripheral blood monocytes were higher in hyperuricemia group(P<0.01).There is no significant difference in the expression of NLRP3,ASC and caspase-1 protein in peripheral blood monocytes(P>0.05).The expression of inflammatory factors IL-1β and IL-18 was significantly increased in hyperuricemia group(P<0.01).Compared with the control group,blood creatinine,urea nitrogen,uric acid and urine erythrocyte were significantly elevated in gouty nephropathy group(P<0.05).The expression of NLRP3,ASC,caspase-1 mRNA and NLRP3,ASC protein in peripheral blood monocytes were higher in gouty nephropathy group(P<0.05).The expression of inflammatory factors IL-1β and IL-18 was significantly increased in gouty nephropathy group(P<0.01).Compared with the hyperuricemia group,there is no significant difference in the expression of blood creatinine,urea nitrogen and uric acid in gouty nephropathy group(P>0.05).Urine erythrocyte was significantly elevated in gouty nephropathy group(P<0.05).The expression of ASC,caspase-1 mRNA and ASC protein in peripheral blood monocytes were higher in gouty nephropathy group(P<0.05).The level of IL-1β also significantly increased in gouty nephropathy group(P<0.05).ConclusionsDuring the renal damage caused by hyperuricemia,we observed a significant increase in the expression of peripheral blood monocytes NLRP3、ASC、caspase-1 mRNA and NLRP3、ASC、caspase-1 protein in NLRP3 inflammasome signaling pathway,as well as the plasma inflammatory factors IL-1β and IL-18,indicating that monosodium urate stimulates the activation of NLRP3 inflammasome and the release of inflammatory factors to take part in the immune response,mediating the inflammatory response and renal damage,which plays an important role in the progression of gouty nephropathy.