五味子乙素对胰腺癌恶性进展小鼠模型的影响及炎症机制OA

Objective:To investigate the effects of Schisandrin B on the malignant progression of pancreatic cancer in a transgenic mouse model with pancreatic cancer and its underlying mechanism.Methods:LSL-KrasG12D/+mice were bred with Pdx1-Cre mice to generate LSL-KrasG12D/+;Pdx1-Cre(KC)mice.Then,according to the body weight,KC mice were randomly assigned into blank control group,100 mg/kg Schisandrin B control group,model control group,and 100 mg/kg Schisandrin B intervention group,with 6-7 mice per group.The model and intervention groups received intra-peritoneal injections of caerulein to induce a pancreatic cancer progression model.The Schisandrin B control group was administered with Schisandrin B,once a day for 4 weeks,while the Schisandrin B intervention group was administered with Schisandrin B at the same time as modeling.After the last administration,pancreatic tissue was collected and weighed to calculate the pancreatic index.HE staining was used to assess pathological changes in pancreatic tissue,while Masson staining was used to evaluate the extent of fibrosis.Alcian blue staining was used to determine the expression of acidic mucoproteins.Immunohistochemical(IHC)staining was used to assess the positive area or the number of positive cells for α-SMA,CK-19,and Ki67.The levels of IL-6 and IL-1β in pancreatic tissue were detected by enzyme-linked im-munosorbent assay.Immunofluorescence(IF)staining was used to observe the expression distribution of NF-κB protein in pancreatic tissue;Western blot method was employed to detect the expression level of NF-κB protein in pancreatic tis-sue.Results:Compared with the blank control group,the Schisandrin B control group showed a significant reduction in the positive areas of Alcian blue and CK-19 in the pancreatic tissue(P＜0.05).Compared to that in the blank control group,pancreatic mass and index were significantly increased in the model group(P＜0.01),with acinar cells exhibiting disordered arrangement,blurred boundaries,severe vacuolar degeneration,extensive inflammatory cell infiltration,and pronounced fibrosis.The number of Ki67-positive cells,as well as the positive area of α-SMA and Masson were signifi-cantly increased(P＜0.01),and the levels of IL-1β and IL-6 were increased(P＜0.01).The expression level and nu-clear translocation of NF-κB protein were significantly increased(P＜0.01).Compared to the model control group,the Schisandrin B intervention group exhibited significantly reduced pancreatic mass and index(P＜0.01).Acinar cells were more tightly arranged with clear boundaries,and reduced vacuolar degeneration,minimal inflammatory cell infiltra-tion,and less fibrosis were observed.The number of Ki67-positive cells,as well as the positive areas of Masson staining and α-SMA staining were increased(P＜0.01),and the levels of IL-1β and IL-6 were decreased(P＜0.01).The ex-pression level and nuclear translocation of NF-κB protein were significantly decreased(P＜0.01).Conclusions:Schisandrin B effectively inhibits the malignant progression of pancreatic cancer.The mechanism of action is related to inhibiting the expression of NF-κB protein and nuclear translocation,reducing the secretion of pro-inflammatory factors,reshaping the inflammatory microenvironment,and thus inhibiting the proliferation of cancer cells and stellate cell activa-tion.