Therapeutic effect and mechanism of Dahuang Fuzi decoction on severe acute pancreatitis in mice
Objective To explore the therapeutic effects of Dahuang Fuzi decoction(DHFZT)on severe acute pan-creatitis(SAP)in mice through the establishment of mouse model with SAP.Methods The SPF mice were randomly di-vided into three groups:control group,model group,and DHFZT group,with 8 mice in each group.Except for the control group,the rat SAP models were established in each group by intraperitoneal injection of L-arginine.Mice in the the DH-FZT group received oral administration of 1.5 mL DHFZT at 6 and 12 h after modeling,while mice in the control and mod-el groups received oral administration of 1.5 mL normal saline.Following the final oral administration,anesthesia was ad-ministered to collect eye samples from all mice for ELISA detection of SAP markers such as amylase(AMS)and lipase(LPS),as well as inflammatory response markers including tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Tissue samples from pancreas,lungs,and colon were collected for histological observation and calculation of histological scores.Immunohistochemistry and Western blotting were used to detect α-defensin 6(DEFA6)protein and glucose regula-tor protein 78(GRP78)in small intestine tissues,respectively;immunofluorescence staining was performed to detect lyso-zyme in the small intestine tissues.Results Serum AMS,LPS,TNF-α,IL-6 level were as follows:model group>DH-FZT group>control group(all P<0.05).In the control group,the tissue structures of pancreas,lung and colon were in-tact,and no inflammatory cell infiltration was observed.In the model group,the tissue structures of pancreas,lung and co-lon were destroyed,and red blood cell exudation and inflammatory cell infiltration were observed.The histopathology of DHFZT group was improved compared with that of the model group.The histopathological scores of pancreas,lung and co-lon were as follows:model group>DHFZT group>control group(all P<0.05).Small intestine DEFA6 protein expression was as follows:model group<DHFZT group<control group,GRP78 protein expression was in the following order:model group>DHFZT group>control group,and the relative fluorescence intensity of lysozyme was as follows:model group<DHFZT group<control group(all P<0.05).Conclusion The intragastric administration of DHFZT exhibits specific therapeutic effects on SAP in mice,potentially by inhibiting endoplasmic reticulum stress in Paneth cells,enhancing the secretion of antibacterial molecules,and thus improving intestinal barrier function.