Effect of pioglitazone on oxazolone-induced colitis in mice / 中华消化杂志

ABSTRACT

Objective To investigate the effect of pioglitazone on oxazolone-induced colitis and to clarify the mechanism of apoptosis by Fas/Fas ligand(FasL). Methods Eighteen BALb/c mice of ulcerative colitis induced by oxazolone enema were equally allocated into 3 groups. The mice in group 1 were sacrificed 3 days after enema,lamina propria mononuclear cells(LPMC) were isolated from freshly obtained colonic specimens and treated in vitro with pioglitazone (40 ?mol/L),the annexin-V-FITC was used for detection of apoptosis,and Fas/FasL expression was assayed by flow cytometry. Meanwhile,untreated mice were served as normal controls. Mice in group 2 (control group) and 3 (experiment group) were treated with methylcellulose or pioglitazone(20 mg?kg -1 ?d -1 ) 3 days after enema and were administrated for consecutive 7 days. The colonic inflammation including disease activity index (DAI),macroscopic and histological changes,myeloperoxidase(MPO) activity and levels of interleukin (IL)-4,IL-5 were evaluated. Results Apoptosis of LPMC,expression of Fas and FasL in normal and colitis mucosa were 12.89?1.23,70.63?6.24,8.59?5.47 and 4.25?0.84,62.60?5.85,23.75?10.23,respectively. After treated with pioglitazone,both apoptosis of LPMC and expression of Fas increased,while FasL expression decreased (40.58?10.32,83.98?11.38 and 10.04?5.21 respectively). In group 2 and group 3,the macroscopic and microscopic score,MPO activity,IL-4 and IL-5 level were 2.50?0.55,8.83?0.75, 3.81?0.17,216.46?34.32,102.28?25.74 and 0.33 ?0.52,4.00?0.63,1.25?0.16,179.36?18.15,61.65?17.45,respectively. Conclusion The results indicate that pioglitazone treatment can significantly attenuate colonic inflammation,and it might be related to the apoptosis of LPMC through Fas and FasL.