Effect of emodin on regulatory T cell/T helper 17 cell balance in mice with severe acute pancreatitis and related mechanism

Abstract:

Objective：To investigate the effect of emodin on regulatory T cell（Treg）/T helper 17 cell（Th17） balance in mice with se－vere acute pancreatitis and the possible mechanism. Methods：A total of 60 C57BL/6 mice were divided into normal control group，model control group，and drug group using a random number table，with 20 mice in each group. Cerulein combined with lipopolysac－charide was used to establish a mouse model of severe acute pancreatitis. After the model was established successfully，the mice in the drug group were given intraperitoneally injected with emodin at a dose of 2.5 mg/kg/day，and those in the model control group and the normal control group were given normal saline at the same dose. The mice were sacrificed after anesthesia at 48 hours after ad－ministration. ELISA was used to measure the serum levels of amylase，lipase，tumor necrosis factor-α（TNF-α），diamine oxidase （DAO），and interleukin-10（IL-10）；flow cytometry was used to measure the percentages of Treg cells and Th17 cells in the spleen；q-PCR was used to measure the mRNA expression of forkhead or winged helix transcription factor（Foxp3），retinoid acid-related or－phan receptor gamma t（RORγt），and Toll-like receptor 4（TLR4） in the spleen. Results：Compared with the normal control group，the model control group had significant increases in the serum levels of lipase，amylase，TNF-α，DAO，and IL-10，the mRNA expression of Foxp3，RORγt，and TLR4，and the number of Treg and Th17 cells，as well as a significantly greater increase in the percentage of Th17 cells and a significant reduction in Treg/Th17 ratio（all P<0.05）. Compared with the model control group，the drug group had significant reductions in the serum levels of lipase，amy－lase，TNF-α，DAO，and IL-10，the mRNA expression of Foxp3，RORγt，and TLR4，and the number of Treg and Th17 cells and a significant increase in Treg/Th17 ratio（all P<0.05）. Conclusion：Emodin can significantly reduce the expression of TNF-α，DAO，and IL-10 and relieve inflammatory stress and oxidative stress response. It can also regulate Treg/Th17 balance，improve immune disorders，and thus play a role in the treatment of severe acute pancreatitis.