Experimental study on the effect of triptolide on acute pancreatitis by regulating IL-34/CSF-1R/STAT3 signaling pathway

Objective To investigate the expression characteristics and potential molecular mechanisms of interleukin-34 (IL-34) in the early inflammatory response of acute pancreatitis (AP), and to evaluate the intervention effect of Celastrol on this inflammatory process.Methods A total of 18 SPF male SD rats were randomly divided into control group (Sham group), AP group and Celastrol+AP group, with 6 rats in each group. In vitro experiments, AR42J pancreatic acinar cells were divided into control group (Con group), AP group and Celastrol+AP group, and samples were collected after 24 hours of treatment. The levels of IL-6, TNF-α, IL-34 and amylase in serum and cell supernatant were measured, respectively. HE staining was used to evaluate the pathological changes of pancreatic tissue. Western blot, immunohistochemistry and immunofluorescence were used to detect the expressions of IL-34, CSF-1R and p-STAT3 proteins.Results Compared with the control group, the expression of IL-34 protein in pancreatic tissues and AR42J cells in the AP group was significantly up-regulated (P<0.05), while the expression of CSF-1R protein and the phosphorylation level of STAT3 were significantly increased (P<0.05), and the levels of IL-6, TNF-α and IL-34 in serum and supernatant were also significantly increased (P<0.05). Celastrol treatment significantly inhibited the expression of the above proteins (P<0.05), and the levels of inflammatory factors in serum and cell supernatant were also significantly reduced (P<0.05).Conclusion IL-34 is involved in the occurrence and development of early inflammatory response in AP, and Celastrol alleviates the early inflammatory response in AP by inhibiting IL-34/CSF-1R/STAT3 signaling pathway, thus having a certain protective effect on AP.