甘草酚调节JAK2/STAT3信号通路对炎症性肠病小鼠肠黏膜损伤的影响研究OA

Objective To investigate the effect of glycyol on intestinal mucosal injury in mice with inflammatory bowel disease by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods Thirty-six male C57BL/6J mice aged 6-8 weeks were randomly divided into four groups by the random number table method:control group,inflammatory bowel disease group,glycyol treatment group,and glycyol+activator group,with 9 mice in each group.The inflammatory bowel disease model was established by administering 3.0％(w/v)dextran sulfate sodium in drinking water.Mice in the control group,inflammatory bowel disease group,glycyol treatment group and glycyol+activator group received drinking water without dextran sulfate sodium,dextran sulfate sodium in drinking water,dextran sulfate sodium daily combined with intraperitoneal injection of 10 mg/kg glycyol,and dextran sulfate sodium daily combined with intraperitoneal injection of 10 mg/kg glycyol and 2 mg/kg RO8191(a JAK2 activator),respectively.All treatments were administered for seven consecutive days.On day 8,mice were sacrificed by cervical dislocation,and colon tissues were collected.The levels of inflammatory cytokines including interleukin(IL)-1 β,tumor necrosis factor-α(TNF-α),IL-6,and IL-10 in colon tissues were detected by enzyme-linked immunosorbent assay.Colon morphology was assessed by hematoxylin-eosin(HE)staining.Cell apoptosis in colon tissues was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay.The expression of zonula occludens-1(ZO-1)protein was detected by immunofluorescence staining.The expression of JAK2/STAT3 signaling pathway-related proteins in mouse colon tissues was determined by Western blotting.Results Compared with the control group,the inflammatory bowel disease group showed significantly increased levels of IL-1β,TNF-α,IL-6,HE staining histological score,TUNEL positivity ratio,and phosphorylated-JAK2(p-JAK2)and phosphorylated-STAT3(p-STAT3)proteins expressions in colon tissues(all P＜0.05),while the IL-10 level and ZO-1 protein expression were significantly decreased(both P＜0.05).Compared with the inflammatory bowel disease group,the glycyol treatment group exhibited significantly decreased levels of IL-1 β,TNF-α,IL-6,HE staining histological score,TUNEL positivity ratio,and p-JAK2 and p-STAT3 protein expressions,along with significantly increased IL-10 level and ZO-1 protein expression(all P＜0.05).Administration of JAK2 activator RO8191 significantly upregulated p-JAK2 and p-STAT3 proteins expressions(all P＜0.05)and reversed the protective effects of glycyol on intestinal mucosal injury in mice.Conclusion Glycyol may alleviate intestinal mucosal injury in mice with inflammatory bowel disease by inhibiting the JAK2/STAT3 pathway.