Exploring Mechanism of Modified Fuzi Lizhongtang in Intervening Inflammatory Response of Intestinal Mucosa in Rats with Ulcerative Colitis Based on mTOR/p-S6K1 / 中国实验方剂学杂志

ABSTRACT

Objectives:To investigate the therapeutic effect and mechanism of modified Fuzi Lizhongtang on ulcerative colitis （UC） model rats. Method:The 72 male SD rats were randomly divided into normal group，model group，sulfasalazine group（0.5 g·kg-1），modified Fuzi Lizhongtang high，medium and low-dose group （23.62，11.81，5.91 g·kg-1）. These rats were used to replicate the UC rat model by 2，4，6-trinitrobenzene sulfonic acid （TNBS）-ethanol composite modeling and treated by gavage for 2 weeks. The general condition of rats in each group was observed. After anesthesia，blood was collected from abdominal aorta and colonic tissue was taken. Semi quantitative evaluation by the colon mucosa damage index （CMDI），the pathological changes of colonic tissue were observed by the hematoxylin and eosin （HE） staining. The contents of serum interleukin-4 （IL-4），IL-6，IL-10 and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of mammalian target of rapamycin（mTOR） and phosphorylated ribosomal protein S6 kinase 1 （p-S6K1） in colonic mucosa were detected by immunohistochemistry （IHC） and Western blot. Result:Compared with normal group，the CMDI score of the model group rats was significantly increased （P<0.01）. The contents of IL-4 and IL-10 in serum were significantly decreased，the contents of IL-6 and TNF-α were significantly increased （P<0.01）. The expression levels of mTOR and p-S6K1 in colonic mucosa were up-regulated （P<0.01）. Compared with model group，the CMDI score of the modified Fuzi Lizhongtang high dose group was significantly decreased （P<0.05）. In modified Fuzi Lizhongtang high and medium dose group，the contents of IL-6 and TNF-α were significantly decreased （P<0.01） and the contents of IL-4 and IL-10 in serum were significantly increased （P<0.05，P<0.01）. In the modified Fuzi Lizhongtang high dose group，the expression level of mTOR and p-S6K1 protein was down-regulated significantly （P<0.05，P<0.01）. Conclusion:Modified Fuzi Lizhongtang high dose group can significantly reduce the congestion and edema，inflammatory cell infiltration，gland distortion，disorder of arrangement and other pathological manifestations of UC colon mucosa，and its mechanism may be related to its down-regulation of mTOR/p-S6K1 signal and the regulation of inflammatory factors secretion.