Exploration on the mechanism of action of Qingjie Huagong Decoction on the inflammatory response of severe acute pancreatitis based on the P2X7R/TLR4/NF-κB/NLRP3 axis
Objective:To study the mechanism of P2X7R/TLR4/NF-κB/NLRP3 axis in the inflammatory response of severe acute pancreatitis(SAP)and the interventional effect of Qingjie Huagong Decoction(QJHGD).Methods:A SAP rat model was established by using cerulein combined with lipopolysaccharide.A blank group,a model group,a group administered with different dosages of QJHGD,and a positive control group were set up,and the histopathology of the pancreas was observed by HE staining,the inflammation indexes were detected by ELISA,and the expressions of P2X7R,TLR4,NF-κB and NLRP3 proteins and mRNAs were detected by combining with Western Blot and qRT-PCR in pancreatic tissues.Results:Compared with the blank group,pancreatic tissue edema,necrotic hemorrhage,serum levels of IL-8,IL-12,IL-17 and IL-18 in the model group were significantly higher(P＜0.05),and the expression of P2X7R,TLR4,NF-κB,NLRP3 proteins and mRNAs in pancreatic tissues were significantly higher(P＜0.05).Compared with the model group,the QJHGD dose groups and positive control group could improve the edema of SAP pancreatic tissues,reduce necrotic hemorrhage,and could reduce the serum levels of IL-8,IL-12,IL-17 and IL-18 in SAP model rats(P＜0.05),and the expressions of P2X7R,TLR4,NF-κB,NLRP3 protein and mRNA in pancreatic tissues of medium and high dose groups and positive control group were decreased(P＜0.05).Conclusion:The QJHGD may play a role in the treatment of SAP by down-regulating the expression of the P2X7R/TLR4/NF-κB/NLRP3 signaling pathway,thereby controlling the inflammatory response to SAP.
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