The Role Of PPARγ Signalling In The Therapeutic Mechanism Of Tetramethylpyrazine Treating Ulcerative Colitis

Background & Aims: Ulcerative Colitis(UC) is a chronic idiopathic inflammation of the gastrointestinal tract. Etiology and pathogeny of UC are still unknown and there are no important breakthroughs of its treatment. It was recently reported that tetramethylpyrazine (TMP) can decrease the degree of inflammation associated with ulcerative colitis. Peroxisome proliferators activated receptors (PPARs) are members of the nuclear receptor family, activated by a diverse class of lipophilic compounds. Recently substantial evidence suggested that PPARγplay an important role in the inflammation of UC. In this study, our aim is to approach the role PPARγsignalling in the mechanism of TMP pharmacologic effect on oxalzolone induced colitis.Methods: Mice UC model were induced by oxazolone ,and randomized into five groups : 50% ethanol infused normal control group(NC), UC group(OXZ) ,TMP treated group(TMP), the specific PPARγantagonists BADGE treated group(BA) and BADGE&TMP group(TMP&BA). Disease active index (DAI) ,macroscopic and histological damage were observed and evaluated .Colonic MPO was measured by chemical method .The mRNA level of PPARγ,NF-κB p65 iNOS,COX-2,and TNF-αin colonic mucosa were quantitated by real-time PCR .The protein level of PPARγ,NF-κB p65 was detected by immunohistochemistry. Phosphorated p38 MAPK were measured by Western blotting.Results: Compared with NC group, the expression of PPARγwas decreased in OXZ group but NF-κB p65,TNF-αwere higher (P<0.01). Both symptoms and the lesions of colonic mucosa were slighter in the animals treated with TMP than those of OXZ group(P<0.01).And the expression of PPARγwas significantly increased in TMP group than NS group(P<0.01), but NF-κB p65,TNF-αwere decreased(P<0.01). The DAI, and the activity of MPO, NF-κB p65, p-p38 MAPK in the colon tissues of the mice in the BA group were significantly increased(P<0.01),with negatively stained PPARγin BA group mouse. As compared with BA group, the result of immunohistochemistry showed the expression of PPARγin TMP&BA group was significantly increased , the DAI, and the activity of MPO, NF-κB p65, p-p38 MAPK in the colon tissues of the mice in the TMP&BA group were all significantly decreased(P<0.01).Conclusions: PPARγcan be impaired in oxalzolone induced colitis , Blockade of PPARγsignalling could aggravate the inflammation of colon mucosa. It indicates that PPARγsignalling involves in the development of ulcerative colitis. TMP could downregulate the expression of PPARγ, and counteract the effect of PPARγsignalling. The effect of TMP treated in UC might be related to PPARγsignalling, but is independent of PPARγ.