Mechanism of Qingyi decoction in inhibiting the expression of nod like receptor family Pyrin domain protein 3 of peritoneal macrophages and reducing acute pancreatitis associated lung injury
ZHANG Xiang-qun,PAN Jian-hong,LI Xiao
Abstract:
Objective To investigate the mechanism of Qingyi decoction in reducing acute pancreatitis (AP)-related lung injury based on the expression of NOD like receptor family Pyrin domain protein 3 (NLRP3) of peritoneal macrophages. Methods Thirty SPF male SD rats were randomly divided into control group, AP group and AP+Qingyi decoction group, with 10 rats in each group. AP model was induced by intraperitoneal injection of cerulein combined with lipopolysaccharide (LPS). Rats in AP + Qingyi decoction group were given Qingyi decoction (17.136 g/kg) by gavage 3 h before the first injection of cerulein and 9 h after LPS injection. Twelve hours after the successful preparation of the model, the serum amylase activity and lung surfactant protein A (SP-A) content of rats in each group were detected, and the histopathological changes of pancreas and lung were observed; Peritoneal macrophages were isolated by peritoneal lavage for transcriptomic sequencing, and verified by fluorescent quantitative PCR and Western blot; The levels of IL-1 β and IL-18 secreted by peritoneal macrophages were detected by ELISA. Results Compared with the AP group, the pathological injury of pancreas and lung tissue, and serum amylase activity were decreased, the serum SP-A content was increased in the AP+Qingyi decoction group(P <0.05). Transcriptomic analysis found 328 common differential genes in the three groups. KEGG pathway enrichment analysis and validation results showed that NLRP3 expression was up-regulated in AP group and down regulated in AP+Qingyi decoction group (P <0.05). Compared with the AP group, the levels of IL-1β and IL-18 secreted by peritoneal macrophages in the AP+Qingyi decoction group were decreased (P <0.05). There was a positive correlation between pancreatic histopathological score and NLRP3 expression, between NLRP3 expression and lung histopathological score. Conclusion The mechanism of Qingyi decoction in alleviating AP associated lung injury is related to inhibiting the expression of NLRP3 of peritoneal macrophages and reducing the production of inflammatory cytokines.
