Study On The Mechanism Of Exercise Through Up-Regulating PPAR-γ To Regulate TSLP To Aggravate Ulcerative Colitis

Objective: In recent years,with the change of western diet,the prevalence and incidence of inflammatory bowel disease(IBD)is increasing.Obesity has become a great threat to IBD.IBD mainly includes ulcerative colitis(UC)and crohn’s disease(CD).Clinically,we found that intestinal inflammation was reduced after exercise,but the mechanism was not clear.thymic stromal lymphopoietin(TSLP),as a new type of cytokine,is still controversial in its anti-inflammatory and pro-inflammatory effects in IBD.To observe the effect of exercise on dextran sodium sulfate(DSS)-induced ulcerative colitis in mice and explore the role and mechanism of TSLP in ulcerative colitis.Methods: Sixty-eight week-old Balb / c mice were selected and randomly divided into sedentary(SED)control group,SED + DSS group,SED + GW9662 + DSS group,SED+ pioglitazone + DSS group,exercise(EXE)control group,EXE + DSS group,EXE +GW9662 + DSS group,EXE + pioglitazone + DSS group after one week of adaptive feeding,8 animals in each group.The mice in each group exercised on the treadmill for40 minutes every day.The sedentary groups were not exercised.The mice in the SED +GW9662 + DSS group and the EXE + GW9662 + DSS group were intraperitoneally injected with GW9662(PPAR-γinhibitor,1 mg / kg / alternate day).Mice in the SED +pioglitazone + DSS group and the EXE + pioglitazone + DSS group were administrated with pioglitazone(10mg / kg / day).After the 30-day exercise period and drug treatment,except for the SED control group and the EXE control group,the rest Mice in each group were given free drinking of 3% DSS solution for 7 days.The weight changes of mice were weighed regularly,and their mental status,hair and diet were recorded.Mice were sacrificed after fasting for 24 hours,and serum and colon tissue were collected for later use.The disease activity index and the histopathological changes of the colon were used to assess the degree of inflammation.The serum inflammation indicators(IL-6,IL-1β)and TSLP secretory condition were detected by ELISA.The expression of PPAR-γmRNA in colon tissue was detected by RT-PCR.Results: Disease activity index and colon histopathology scores of mice in each exercisegroup were higher than those in the corresponding sedentary group;IL-6 secretory condition in serum was higher in each exercise group than in the corresponding sedentary group(P <0.05);The secretory condition of IL-1β in each exercise group was higher than that in the corresponding sedentary group.There was a statistically significant difference between the SED + GW9662 + DSS group and the EXE + GW9662 + DSS group(P <0.05);except for the control group,the secretory condition of TSLP in serum was different in each exercise group.The groups were lower than the corresponding sedentary group(P <0.05);with each sedentary group as a control,the relative expression of PPAR-γ mRNA in the corresponding exercise group was increased(P <0.05).Conclusion: TSLP plays a protective role in UC,and exercise increases the occurrence of UC by up-regulating PPAR-γ and down-regulating TSLP.