Mechanism of Wumei (乌梅) Pills in Restoring Intestinal Mucosal Barrier in Mice with Ulcerative Colitis Based on P38MAPK Signaling Pathway
Objective:To investigate the mechanism of Wumei (乌梅) Pills in restoring intestinal mucosal barrier injury in mice with ulcerative co-litis (UC) based on the p38 mitogen activated protein kinase (P38MAPK) signaling pathway.Methods:Forty C57BL/6 mice were randomly divided into normal control group,model control group,mesalazine (0.5 g/kg) group,and Wumei Pill groups of 13.04 g/kg and 26.09 g/kg.The mice of the normal control group had free access to water,while the mice of the modeling groups had free access to 2％ dextran sodium sulfate (DSS) aqueous solution.At the same time,mice in the normal control group and model control group were orally administrated with normal saline,while mice in the administration groups were orally administrated with corresponding medication.The disease activity index (DAI) of the mice was evaluated.Hematoxylin-eosin (HE) staining was used to observe and score the histopathological score (HS) of the colon.The levels of diamine oxidase (DAO) and D-lactate in the serum of the mice were measured by enzyme-linked immunosorbent assay (ELISA).The mRNA expressions of Occludin-1,Claudin-1,and zonula occludens-1 (Zo-1) in colon tissue were tested by real-time fluores-cence quantification polymerase chain reaction (RT-qPCR).The expressions of Occludin-1,Claudin-1,and ZO-1 in colon tissue,as well as p38MAPK,extracellular signal-regulated kinase (ERK),c-jun N-terminal kinase (JNK) protein,and its phosphorylation products including p-ERK,p-JNK,and p-p38MAPK were tested by western blotting (WB).Results:Compared with the normal control group,the DAI and HE scores and the levels of DAO and D-lactate in peripheral blood were all improved in the model control group from the 4th day of molding (P<0.01).The protein and mRNA expressions of Occludin-1,Claudin-1,and ZO-1 in colon tissue were significantly reduced (P<0.01).The ratios of p-p38MAPK/p38MAPK,p-ERK/ERK,and p-JNK/JNK in colon tissue were significantly increased (P<0.01).Compared with the model control group,the DAI and HE scores were decreased in the Wumei Pill groups (P<0.01 or P<0.05).The protein and mRNA expres-sions of Occludin-1,Claudin-1,and ZO-1 in colon tissue were significantly increased (P<0.01),and the ratios of p-p38MAPK/p38MAPK,p-ERK/ERK,and p-JNK/JNK in colon were significantly decreased (P<0.01).The content of D-lactate in the serum of the Wumei Pill (13.04 g/kg) group,and the contents of DAO and D-lactate in the serum of the Wumei Pill (26.09 g/kg) group were significantly de-creased (P<0.01 or P<0.05).Conclusion:One of the mechanisms of Wumei Pills restoring intestinal mucosal barrier injury in mice with UC may be inhibiting the phosphorylation of p38MAPK signaling pathway protein and increasing the expression of tight junction protein.
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